Chronic pain definition principles of treatment. Principles of chronic pain management

“Pain is the watchdog of health, for it warns of danger,” the ancients said. Pain syndrome occurs in diseases of internal organs, nerves, muscles, joints, spastic and inflammatory processes, tumors, injuries, burns, surgical and diagnostic interventions, and in many other clinical situations. Pain sensations are the most unpleasant signs of illness or injury, the elimination of which has always been associated with high medical art, with the very essence of the medical profession, its humanity. A doctor today knows and can do a lot, his knowledge of diseases is replenished every day, but the cure of many pathological conditions remains an unattainable dream. The greater the success modern medicine in alleviating the suffering of patients, in the treatment of acute and chronic pain. Today we can talk not only about the temporary relief of the suffering of the patient, but about targeted, pathogenetically determined pharmacotherapy of pain.

Previously, pain was considered a special feeling associated with damage to tissues or organs. Today, we invest much more in this concept: pain is an integrative function, in the formation of which many body systems participate, it is designed to signal the action of a factor dangerous for the body, its nature and intensity, and also to mobilize the body's forces to eliminate it. Thus, pain is a complex integrative process, in which consciousness, sensation, memory, motivation, vegetative mechanisms, behavioral reactions and emotions are involved in its occurrence and maintenance. That is why intense acute or long-term chronic pain can significantly burden the existence of the patient, sharply reduce the quality of his life. This problem is most relevant in rheumatology, surgery, and oncology, where pain pharmacotherapy is one of the most serious medical and social problems.
Every doctor should be able to provide effective pain relief, first of all, for reasons of humanity. In addition, there is now ample evidence that pain management is important physiologically for the course of the disease as a whole.
For example, pain associated with surgery chest or abdominal cavity, contributes to the occurrence and aggravation of impaired lung function, muscle tone of the abdomen and diaphragm. Due to severe pain, the patient cannot fully move, breathe deeply and rhythmically enough, cough up sputum, which can lead to atelectasis and pneumonia. Pain activates the sympathoadrenal system, which causes tachycardia, an increase in oxygen consumption by the myocardium. Prolonged pain also reduces physical activity, and involuntary physical inactivity can lead to venous congestion, an increased risk of deep vein thrombosis and pulmonary embolism. Perhaps an adverse effect on intestinal motility, urinary tract, which, in turn, contributes to postoperative intestinal paresis, nausea, vomiting and urinary retention. Timely and sufficient pain relief can reduce the incidence of complications, alleviate the course of the disease, and prevent the development of chronic pain syndromes.
Another example concerns the chronic pain syndrome that accompanies malignant neoplasms. The quality of life and the results of treatment of any oncological disease cannot be assessed without taking into account the dynamics of chronic pain syndrome. It is well known that in the majority of cancer patients in the terminal period, pain is the main and very painful symptom of the tumor. In this case, it loses its biological protective role, becomes an additional damaging factor and is accompanied by a number of secondary disorders in the patient's body. The treatment of physical and mental suffering that occurs as a result of chronic pain is a very complex and multifaceted task that requires the participation of a whole team of specialists (radiologists, surgeons, chemotherapists, neuropathologists, pharmacologists, anesthesiologists, psychotherapists). At the same time, in real clinical practice, providing assistance to patients of the IV clinical group - with advanced forms malignant tumor and irreversible progression of the disease - mainly the lot of local therapists, family doctors, nurses, ambulance services.
The importance of treating pain in this case is so high that often the management of terminal oncological patients is reduced to the appointment of narcotic analgesics. Such treatment brings temporary relief, but is fraught with negative consequences- rapid addiction to strong painkillers, the ineffectiveness of weaker ones, the need to constantly increase the doses of drugs. In addition, a number of financial and organizational problems in our country make it difficult to effectively treat cancer patients in the terminal stage of the disease. Such patients, as a rule, are left alone with the disease. The hospice system is already developing in Ukraine, but is not yet able to solve all the problems of cancer patients in the terminal stage. At the same time, a competent and balanced approach to pain relief, even such chronic progressive pain as cancer, can significantly alleviate the patient's suffering. Timely communication between narrow specialists, good contact with the patient and his relatives, knowledge of the pathogenesis of pain and modern methods of treatment open up new opportunities for doctors. Elucidation of the pathogenesis, recording the type of pain, its dynamics, building a clear plan of therapeutic measures and their active control is an essential component of modern clinical oncology.

So, what should every doctor know about proper pain relief? According to WHO recommendations, modern pain relief is based on a three-stage (sequential) scheme. The logical strategy for treating pain is as follows: the use of a complex of drugs at one stage is carried out until the effect of simpler analgesics is exhausted, then they move on to the next stage, up to strong drugs with potentiation. This tactic allows achieving satisfactory pain relief in 88% of cases.

First stage
At the first stage of pain relief (for mild to moderate pain), it is recommended to use analgin, paracetamol, acetylsalicylic acid, salicylamide, acetaminophen, indomethacin, indocid, orthophene, mefenamic acid, brufen, naproxen, butadione and other non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of action of NSAIDs is to inhibit the synthesis of prostaglandins by inhibiting cyclooxygenase, which is involved in the breakdown of arachidonic acid into various prostaglandins, which are the main mediators of inflammation. All NSAIDs work in the same way, so they are not usually prescribed in combination with each other, but it is important to note the high effectiveness of the combination of NSAIDs with opioids due to differences in their mechanism of action. The drugs of this group can be used both for short-term pain relief (for example, postoperative) and for the treatment of chronic pain. The advantages of non-opioid analgesics include a wide range of dosages and forms of drug administration (tablets, capsules, injections, creams and suppositories), thanks to which you can individually select the optimal regimen, as well as a number of additional effects (anti-inflammatory, antipyretic, antiplatelet, immunomodulatory). It should be noted that the importance of using NSAIDs in the treatment of pain is often underestimated, meanwhile, drugs in this group are considered effective analgesics for mild, mostly superficial pain emanating from the skin, mucous membranes, joints or bones, and in combination with narcotic analgesics - and with moderate pain; they are widely available throughout the world, effective when taken orally.
There is wide variation in individual response to these medicines, so there is no drug of choice as such. The choice of NSAIDs depends on what caused the pain, how long it lasts, on the patient's individual response to a particular drug, and other factors. For example, if the pain is expected to last for a long time, it is better to choose a drug with a long clinical effect.
However, this group of drugs has a high percentage of side effects with long-term use, so their appointment for a long time should be approached with caution. So, most NSAIDs have an antiplatelet effect, which means they increase bleeding time. The most dangerous effect of non-selective NSAIDs is the inhibition of prostaglandin synthesis in the gastric mucosa, which manifests itself in the form of complications from the gastrointestinal tract. They should be used with caution in patients with bronchial asthma and impaired renal function. Each NSAID has its own frequency of adverse reactions and its own set of these reactions. For example, aspirin, in addition to these side effects, has a significant association with Reye's syndrome and should not be used for analgesia in children under 12 years of age.
For all categories of patients, one should not strive for pain relief by an indefinite increase in dose, since in this case the risk of severe complications significantly exceeds the gain in analgesia. In patients over 60 years of age (especially heavy smokers) who have previously been treated for peptic ulcer with long-term ingestion of large doses of NSAIDs against the background of steroid hormones or anticoagulants, the prophylactic administration of ranitidine or omeprazole is justified - this significantly reduces the risk of acute erosions and ulcers of the gastrointestinal tract.
The dose of analgesic must be selected individually for each patient. Oral administration is preferred because parenteral drug administration requires specially trained personnel. Sometimes the most appropriate way to administer an analgesic is transrectal, in the form of suppositories. For patients suffering from indomitable vomiting and a number of other disorders, parenteral administration is preferable.
In patients with mild pain, aspirin can be quite effective, and if it is intolerant, paracetamol can be effective. They have a beneficial effect on pain caused by bone metastases, stretching of the periosteum, involvement of muscles and tendons, peritoneum or pleura in the process. If the drug from the NSAID group is not effective enough, you should not immediately switch to drugs. First of all, a more potent agent from this group is prescribed, and the dose of the drug and its regimen are adjusted. So, it should be remembered that often the pain intensifies at night. Therefore, at night it is recommended to increase the dose of the analgesic, which makes it possible to increase the period with a reduced level of pain, improve the patient's sleep. The first and last doses during the day should be timed to the awakening of the patient and the time of going to bed, respectively. In general, the regimen of taking analgesics is very important: if pain relief is prescribed regularly, at strictly defined hours, then the patient more calmly tolerates the natural increase in pain by the end of the drug; in the case of the “on demand” regimen, the time between analgesic doses is progressively reduced, and the doses of the drug increase unnecessarily quickly.

Second step
If regular and correct application NSAIDs do not provide adequate pain relief, then, according to WHO recommendations, they move on to the second step of the analgesic ladder - the appointment of weak drugs (codeine, dihydrocodeine, dextropropoxyphene). In this case, it is first recommended to add them to the first stage drugs. Combined application significantly increases the effectiveness of each drug. Specially created combined forms combine various effects that sum up and potentiate each other.
So, for example, Spasmo-Proxyvon (Wockhardt Limited) is a combination drug that includes three active ingredients - dextropropoxyphene hydrochloride (65 mg), paracetamol (400 mg) and dicyclomine hydrochloride (10 mg). Dextropropoxyphene has a direct analgesic effect, is structurally similar to methadone and belongs to weak narcotic analgesics. It is effectively combined with paracetamol, which enhances its effect. However, when using combined drugs the maximum allowable doses of the components are not exceeded. Therapeutic doses of dextropropoxyphene range from 32.5 mg (in combination with paracetamol) to 300 mg per day (as monotherapy).
Paracetamol, enhancing the analgesic effect of dextropropoxyphene, has an antipyretic effect. It is well absorbed oral administration and almost completely metabolized in the liver; has few side effects at normal doses. Dicyclomine hydrochloride is an antispasmodic. The complex action of all three components is pathogenetic and makes it possible to influence various mechanisms involved in the formation and maintenance of the pain syndrome. The clinical use of such combined agents as Spasmo-Proxyvon confirmed their advantages over monotherapy with simple analgesics for minor surgical interventions or outpatient use in cancer patients.
It should be emphasized that dextropropoxyphene as monotherapy is usually prescribed 150 mg 2 times a day, its combination with paracetamol and an antispasmodic allows you to reduce the dose of the drug while maintaining a sufficient effect. Thus, the appointment of the combined drug Spasmo-Proxyvon not only has an effective and multifaceted pathogenetically substantiated effect on the pain syndrome, but also prevents addiction to the narcotic component, while there remains the possibility of further treatment with an increase in the dose of the narcotic analgesic and a later transition to the third stage.

Third step
According to WHO recommendations, the third step of the analgesic ladder is indicated for severe and unbearable pain (primarily coming from deep tissues or visceral organs), which cannot be treated with conventional means. This stage is based on the use of strong narcotic drugs, primarily morphine and its analogues (diamorphine, prosidol, buprenorphine, fentanyl, methadone). As the first line of treatment in this group of patients, it is necessary to prescribe strong drugs in combination with non-opioids of the first stage. The most powerful analgesic effect has a combined regimen, including the constant and modified use of potent opiates, non-narcotic analgesics and ancillary drugs.
The effectiveness of opioids varies greatly from patient to patient, so it is difficult to predict their effect on a case-by-case basis. Often, doctors overestimate the duration of action and potential of these drugs, fear respiratory depression, vomiting, excessive sedation, the development of drug dependence and other complications in patients taking narcotic analgesics, as a result, they underestimate the required dose. Therefore, patient-controlled analgesia (AUA), which has become widespread in the developed world, is always more effective than intramuscular administration of opioids.
The AUB technique became popular when it became clear that individual needs for analgesia vary considerably. With this in mind, a device was designed with which patients can control the level of analgesia themselves using a controlled syringe. In the event of pain, the patient himself injects a small bolus of the opioid and evaluates its effect, that is, he can “tune” the level of analgesia depending on the severity of the pain. Theoretically, the level of the analgesic in the blood remains relatively constant, and the side effects caused by fluctuations in the concentration of the drug in the blood disappear.
Thus, another way to optimize pain relief is a fairly simple method - targeted training of staff in the basics of pain relief, as well as more active involvement of patients themselves in assessing the quality of pain relief. Ideally, every hospital should have a specialist in treatment acute pain dealing with the relevant equipment and staff training. Unfortunately, the equipment for AUB is too expensive, therefore, in the vast majority of cases, it is not available.
Rational anesthesia should include not only analgesics, but also a number of other means and methods of treatment - auxiliary medications, blockade with local anesthetics (especially effective for localized or unilateral pain), psychotherapy, specific anticancer (radiation, chemotherapy, hormonal) therapy, surgical interventions and, of course, constant and comprehensive care in the hospital and at home. Only complex treatment will achieve sustainable and lasting results.

Conclusion
Below are the general principles of rational pain relief in chronic pain syndrome, especially in terminal cancer patients:
in taking analgesics by the hour, and not on demand;
in the appointment of opioid and non-opioid analgesics "in ascending order" - from weak to strong. Strict adherence to the analgesic "ladder" will ensure the correct sequence in the appointment of analgesic drugs, prevent the rapid depletion of the drug reserve;
in strict observance of the regimen and dose;
in the longest possible use of oral medication, especially on an outpatient basis;
in the prevention of side effects of opioid and non-opioid analgesics;
c if the treatment of chronic pain syndrome is ineffective, it is necessary to consult a specialist in palliative care or to a cancer pain center.
The main principle of the treatment of any pain is the maxim: the pain of each patient must be eliminated or alleviated. Although in many cases it is difficult to fully complete this task, but subject to a careful and consistent assessment of the causes of chronic pain syndrome, right choice a variety of analgesic and auxiliary agents, their rational use - an acceptable result can always be achieved.

PAIN IN ONCOLOGY

Pain is a protective function of the body, it is a warning of imminent danger. This is its positive role in the life of any living being. However, in cancer patients, this function of pain loses its significance and manifests itself in the form chronic pain syndrome.

Despite the unequivocal prognosis, the patient needs adequate pain relief in order to prevent the effect of pain on the patient's physical, mental and moral state and to maintain his social activity for as long as possible.

To solve this problem, you need to follow simple rules:

1- taking analgesics strictly on time in compliance with the dosage
2- reception "from weak to strong"
3- use of adjuvant agents
4- Prevention and treatment of side effects rather than giving up pain relief

Rule 1
All analgesics should be taken strictly according to the scheme, and not at the request of the patient. Pain is much easier to prevent than to treat later.
This rule matters only if the dosage is strictly observed.

Rule 2
Reception "weak to strong" implies a three-stage scheme for the use of analgesics, recommended by WHO in 1988
Treatment begins with non-narcotic analgesics until the effect persists, followed by a switch to stronger drugs.

1 step - paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs are also used subsequently at all stages of anesthesia, and are not replaced by stronger drugs
Paracetamol 500-1000 mg 4 times a day.
Ibuprofen 400-600 mg 4 times a day.
Ketoprofen 50-100 mg 3 times a day.
Ketanov - 10 - 20 mg 3 - 4 times a day (considered one of the strongest in this group)

Side effect non-opioid analgesics:
- paracetamol in case of overdose has hepato- and nephrotoxicity
- NSAIDs can cause gastrointestinal bleeding

2 step - use of weak opioids. Either the addition of codeine-containing agents to the drugs of the first group, or the use of the following drugs:
Tramadol 50 - 100 mg 4 times a day (considered the most powerful analgesic in the group)
Stadol 1-2 mg IM or IV 6-8 times a day
Zoldiar 1 - 2 tablets 4 times a day
Solpadeine 1 - 2 tablets 4 times a day (codeine-containing)

:
- codeine-containing drugs - the choice for patients with shortness of breath
- stadol has a pronounced hallucinogenic effect, but it also has the form of an aerosol for intranasal administration (conveniently)
- zaldiar - complex "tramadol + paracetamol",sold in pharmacies without a prescription
- solpadeine - complex "paracetamol + codeine + caffeine"
- tramadol has a threshold effect at a daily dose of 400 mg. A further increase in dosage does not affect the analgesic effect. If 400 mg of tramadol does not stop the pain syndrome, it is necessary to switch to morphine. The main side effects are nausea, vomiting, and constipation.

3 step - use of narcotic analgesics
Promedol
Omnopon
Morphine - 5-10 mg IM or s / c 6 times a day
Buprenorphine
Fentanyl - used in hospital treatment

Some notes on the drugs of this group:
Morphine is the main drug in this group. It does not have a threshold effect, therefore, it can be used indefinitely + you can increase the dosage (up to 300 mg per day - very carefully).By the way, in Ukraine there are no regulations limiting the dose of drugs. The main danger in increasing the dose of morphine is respiratory arrest (it is necessary to control its frequency), although tolerance to this complication develops very quickly. Drug addiction when using morphine (according to WHO) occurs in 1 patient out of 10,000. Main side effects: nausea, vomiting, constipation (easily stopped by taking laxatives)
- omnopon consists of several opioid components, morphine is about 50%
- promedol and buprenorphine are not effective in chronic pain syndrome, because give a sufficient analgesic effect only at the first injections
- Fentanyl - 100 times stronger than morphine, but has a very short-term effect (up to 20 minutes). There is a skin patch with fentanyl - Durogesic. The effect lasts up to 72 hours.
- MCT continus - morphine in tablet form. It is taken 30 - 60 mg 2 times a day. Produced in a large number of dosages.

P.S. There are conditions in which narcotic analgesics do not have an analgesic effect. These are brain tumors (or metastases to the brain), involvement in the tumor process of the nerve plexuses or roots of the spinal cord. The best remedy for such conditions is dexamethasone (or analogues).

Rule 3
Use of adjuvant agents

Adjuvant - auxiliary means that have their own positive properties, or reduce the side effects of the main treatment, or potentiate the action of the main drugs.
- corticosteroids (dexamethasone) - for neurological pain, bone pain, pain with liver metastases, loss of appetite
- with nausea and vomiting - cerucal, haloperidol, chlorpromazine
- with muscle spasms - diazepam
- for depression - amitriptyline
- for constipation - laxatives
- with convulsions - finlepsin, carbamazepine
- with neuropathic pain, with bone sarcomas and bone metastases - Neuralgin. When using Neuralgin, it is necessary to use a high dosage (from 900 mg per day). Otherwise, the result of the treatment will be minimal.

Let's summarize:

A three-stage scheme for the treatment of chronic pain according to WHO (allows you to achieve satisfactory pain relief in 90% of patients) is as follows:

1 - mild pain - non-narcotic analgesic (NSAID) + adjuvant agents.
2 - moderate pain - a weak opioid such as codeine (or tramadol) + non-narcotic analgesic (NSAID) + adjuvant agents.
3 - severe pain - a strong opioid of the morphine group + non-narcotic analgesic (NSAID) + adjuvant agents.

The scheme shows that non-narcotic analgesics should be used at all stages of treatment.
- At stage 2, the dose of tromadol can be increased up to 400 mg per day, in the absence of the effect of treatment, a further increase in the dose is considered inappropriate. It is necessary to proceed to the 3rd stage of therapy.
Morphine is the main drug of the 3rd stage of therapy.
- It is advisable to switch to non-injection methods of treatment (MCT continus, Durogesic, etc.)

Unfortunately, pain syndrome is a difficult clinical task, and it is not always possible to eliminate it. If the therapy is ineffective, it is possible to change the drug and transfer the patient to the parenteral route of administration of analgesics.

Ca 2+ and K +

2 1 , and inducible - COX 2 2 celecoxib, meloxicam.

Channels, CA 2+

Etiopathogenetic principles for the treatment of chronic pain

The constant increase in the number of patients suffering from chronic pain syndromes and the low effectiveness of symptomatic therapy for chronic pain make it possible to consider pain in such patients not as a symptom that signals damage to organs or tissues, but as a leading syndrome that reflects profound disturbances in the functioning of systems that perform perception, conduction. and analysis of pain signals. Pain, once arising as a result of any damage, leads to serious disturbances in the system of regulation of pain sensitivity, causes psychological disorders, forms in the patient special form pain behavior that persists even when the initial trigger of the pain is removed. Chronic pain is defined by the International Association for the Study of Pain as pain that continues beyond the normal healing period and lasts more than three months. The most common are back pain, headaches, pain in cancer patients, and neuropathic pain.

Depending on the leading etiopathogenetic mechanism, pain syndromes are divided into:

nociceptive (somatogenic) associated with tissue damage (somatic and visceral);
neuropathic (neurogenic), caused by primary dysfunction or structural damage nervous system;
psychogenic, arising from mental disorders.

As a rule, the clinical structure of chronic pain syndrome is heterogeneous and often represents a combination of nociceptive pain, neuropathic pain and psychological pain. Therefore, understanding the pathogenesis of pain and the ability to correctly determine the clinical structure of chronic pain largely affect the effectiveness of the therapy. Therapeutic measures in the treatment of chronic pain syndrome should not be symptomatic, but etiopathogenetic.

The development of nociceptive pain is based on the activation of nociceptors during trauma, inflammation, ischemia, or tissue edema. Clinical examples of such pain are post-traumatic and postoperative pain syndromes, arthritis, myofascial pain syndromes, pain in tumor lesions of tissues, angina pectoris, pain in cholelithiasis, and many others.

The clinical picture of nociceptive pain is characterized by the presence of zones of hyperalgesia (zones with increased pain sensitivity). There are primary and secondary hyperalgesia. Primary hyperalgesia develops in the area of damaged tissues, secondary is localized outside the damage zone, spreading to healthy tissues. The development of the primary is due to the sensitization of nociceptors (increased sensitivity of nociceptors to the action of damaging stimuli). Secondary occurs as a result of sensitization (increased excitability) of nociceptive neurons of the posterior horns of the spinal cord.

Sensitization of nociceptors and the development of primary hyperalgesia in case of tissue damage is noted not only in the skin, but also in muscles, joints, bones and internal organs. Sensitization of nociceptors is a consequence of the release of inflammatory mediators (prostaglandins, cytokines, biogenic amines, neurokinins, etc.), which, through interaction with the corresponding receptors on the membrane of the nociceptive fiber, increase the permeability of cation channels for Na ions.+ , Ca 2+ and K + , which leads to increased excitation of nociceptors and increased nociceptive afferent flow.

A progressive increase in the frequency of action potentials generated by nociceptors is accompanied by an increase in the excitability and reactivity (sensitization) of nociceptive neurons at many levels of the central nervous system. The excitatory effect on the membrane of nociceptive neurons is exerted by glutamate and neurokinins (substance P, neurokinin A, calcitonin-related peptide), which, being excessively released from the central terminals of C-nociceptors, lead to an active intake of Ca 2+ into the cell and the development of prolonged depolarization of central nociceptive neurons. The resulting increased excitability of nociceptive neurons can persist for a long time. An increase in the excitability of nociceptive neurons in the CNS structures leads to reflex activation of motor neurons in the corresponding segments of the spinal cord and prolonged muscle tension, initiating the mechanisms of neurogenic inflammation in them and thereby increasing the afferent flow of nociceptive impulses to the CNS structures. This vicious circle of pain - muscle spasm - pain plays an important role in chronic pain syndromes.

The development of neurogenic (neuropathic) pain syndromes occurs as a result of damage or dysfunction of the structures of the peripheral and / or central nervous systems. The causes of damage to peripheral neuronal structures can be metabolic disorders (diabetic polyneuropathy), trauma (phantom pain syndrome, causalgia), intoxication (alcoholic polyneuropathy), infectious process (postherpetic ganglioneuropathy), mechanical compression (neuropathic pain in oncology, radiculopathy with herniated intervertebral discs ). The most common causes of central neurogenic pain are traumatic injuries of the spinal cord and brain, ischemic and hemorrhagic strokes leading to a deficit in somatosensory sensitivity, demyelinating diseases (multiple sclerosis), syringomyelia, etc. In the clinical picture of neurogenic pain, regardless of etiological factors and the level of damage , as a rule, spontaneous pain is present, violations of tactile, temperature and pain sensitivity are detected in the form of hyperpathy, dysesthesia, allodynia, trophic changes in the skin can be observed, subcutaneous tissue, hair, nails, muscle tone or local autonomic disorders in the form of tissue swelling, changes in dermographism, skin color and temperature.

Damage to the structures of the peripheral nervous system is accompanied by a change in the phenotype of nerve fibers. Nerve fibers become sensitive to minor mechanical influences, spontaneous ectopic activity appears. Ectopic activity occurs due to an increase in the number and change in the structure of sodium channels on the membrane of nerve fibers. It is registered in the zones of demyelination and regeneration of the nerve, neuromas, as well as in nerve cells dorsal ganglia associated with damaged axons. Ectopic discharges have an increased amplitude and duration of the signal, which can lead to cross-excitation in nerve fibers, dorsal ganglion neurons and distortion of the perception of applied stimuli. Simultaneously with the violation of the mechanisms of impulse generation in the peripheral nerve, transsynaptic death of neurons occurs in the central structures of the somatosensory analyzer.

The death of neurons under these conditions is due to the excessive release of glutamate and neurokinins into the synaptic cleft, which have a cytotoxic effect in excess concentrations. The subsequent replacement of dead neurons with glial cells contributes to the emergence of a stable depolarization of the remaining neurons and an increase in their excitability. Simultaneously with the death of nociceptive neurons, a deficiency of opioid, glycine, and GABAergic inhibition occurs, resulting in disinhibition of neurons and the formation of long-term self-sustaining activity.

Under conditions of insufficient inhibition, synaptic interneuronal interactions are facilitated, silent (previously inactive) synapses are activated, and nearby hyperactive neurons unite into a single network with self-sustaining activity. These disturbances in the generation and conduction of an impulse in the peripheral nerves and uncontrolled hyperactivity of the central neurons are the pathophysiological basis of sensory disorders in the form of paresthesia, dysesthesia, hyperpathia, and allodynia. A sensitivity disorder caused by neuropathic pain in case of damage to the peripheral and central structures of the somatosensory analyzer is observed in those parts of the body that correspond to the zones of innervation of the affected formations. For the diagnosis of neuropathic pain, neurological examination with an assessment of the state of somatosensory sensitivity, motor sphere and autonomic innervation.

Psychogenic pain syndromes occur regardless of somatic, visceral or neuronal damage and are largely determined by the involvement of the psyche, consciousness, and thinking in the formation of pain sensations. The determining factor in the mechanism of occurrence of psychogenic pain is the disturbed psychological state of a person with depression, hysteria or psychosis. In the clinic, psychogenic pain syndromes are characterized by the presence of severe, prolonged, debilitating pain, unexplained by any known somatic disease or damage to the structures of the nervous system. The localization of this pain usually does not match anatomical features tissues or areas of innervation, the defeat of which could be suspected as the cause of pain. There are situations in which somatic damage, including disorders of the nerve pathways and centers, can be detected, but the intensity of pain in this case greatly exceeds the degree of damage. As a rule, this is associated with acquired "pain behavior", which is formed in patients with one or another somatogenic or neurogenic pain syndrome. Pain in this case becomes an adaptive reaction, becoming fixed in a stereotypical symptom complex of pain behavior (complaints of pain, groans, facial expressions of the sufferer, limitation of mobility). Such a state is unconsciously perceived by the patient as a gain, diverts attention from unresolved social and psychological problems, and, with the next psychological conflict, can be triggered in the form of already familiar “defensive behavior”. With such pain, the function of the suffering organ can be practically not disturbed.

It should be emphasized that chronic pain syndromes are characterized by a combination of pathophysiological processes, when an additional one, which aggravates the clinical picture of pain, is connected to the leading main mechanism. For example, "articular" pain can be caused not only by inflammation in the joint and periarticular tissues, but also by damage to peripheral nerves, which requires the use of combination therapy. As a rule, more than 1/3 of patients with rheumatoid arthritis are diagnosed with signs of peripheral neuropathy. Neuropathic pain in patients with a rheumatological clinic is often the result of nerve damage in systemic vasculitis, cytostatic therapy, and the occurrence of tunnel syndromes.

A similar combination of somatogenic and neurogenic pain is observed in cancer patients. Neuropathic pain in cancer patients is often the result of tumor invasion of nerve structures, nerve damage during chemotherapy and/or radiation therapy, major traumatic surgery, and metastatic lesions of the nervous system structures. Such combined damage to organ tissues and neuronal formations in cancer patients makes the structure of the pain syndrome complex and requires complex pathogenetically substantiated treatment.

The treatment algorithm for chronic pain should take into account the features clinical picture, be simple, safe and effective. Medicines should be prescribed for a long time and taken strictly according to the schedule in an individual dosage.

The principles of etiopathogenetic therapy for chronic pain include:

suppression of the synthesis and release of algogens in damaged tissues;
limitation of nociceptive afferent impulses from the area of damage in the central nervous system;
activation of the structures of the antinociceptive system;
restoration of mechanisms for controlling the excitability of nociceptive neurons;
elimination of generation of ectopic impulses in peripheral nerves;
elimination of painful muscle tension;
normalization psychological state patient.

Means for suppressing the synthesis and release of algogens in damaged tissues

Non-narcotic analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) have the most pronounced analgesic effect among drugs that reduce the synthesis of algogens. Non-narcotic analgesics and NSAIDs, along with an analgesic effect, have an anti-inflammatory and antipyretic effect. The main mechanism of action of these drugs is associated with their inhibition of the synthesis of prostaglandins. Tissue damage caused by phospholipase A 2 arachidonic acid is released in large quantities from the phospholipids of cell membranes and is oxidized by cyclooxygenase to cyclic endoperoxides, which, under the influence of the enzymes prostaglandin isomerase, thromboxane synthetase, and prostacyclin synthetase, are converted into prostaglandins, thromboxane A2, and prostacyclins, respectively. NSAIDs weaken the synthesis of prostaglandins from arachidonic acid by inhibiting the activity of cyclooxygenase (COX) both in peripheral tissues and in the structures of the central nervous system. There are at least two isoforms of COX - tissue, or constitutional - COX 1 , and inducible - COX 2 , whose production increases with inflammation. Both isoforms of cyclooxygenase are found in both peripheral tissues and CNS cells. Non-narcotic analgesics and most NSAIDs block the activity of both isoforms of cyclooxygenase. For the treatment of pain, both non-selective NSAIDs are used - ibuprofen (Nurofen, Nurofen Plus, etc.), diclofenac, ketoprofen, lornoxicam, and selective COX inhibitors 2 celecoxib, meloxicam.

Ibuprofen preparations (Nurofen, Nurofen Plus) are the "gold standard" for the treatment of diseases of the musculoskeletal system, which occur in the population with a frequency of approximately 56% and are the second most common among acute pain syndromes after headache. Nurofen Plus is a combined drug, the action of which is due to the effects of its constituent ibuprofen and codeine. Ibuprofen - NSAIDs, a derivative of phenylpropionic acid - has an analgesic, antipyretic and anti-inflammatory effect by blocking COX. Ibuprofen reduces the concentration of biogenic amines with algogenic properties, and thus increases the threshold of pain sensitivity of the receptor apparatus. Codeine phosphate is an opium alkaloid of the phenanthrene series, an opioid receptor agonist. Analgesic activity is due to the excitation of opiate receptors in various parts of the central nervous system and peripheral tissues, leading to stimulation of the antinociceptive system and a change in the emotional perception of pain. Codeine reduces the excitability of the cough center; when used together with ibuprofen, it enhances its analgesic effect, which is especially important for pain relief in neurological practice. For adults and children over 12 years of age, the drug is prescribed 1-2 tablets. every 4-6 hours. The maximum daily dose is 6 tab.

When choosing an NSAID, it is necessary to take into account its safety, age of patients and the presence of concomitant pathology. It is desirable to use NSAIDs at the lowest dose that provides pain relief, and not to take more than one NSAID at the same time.

Means that limit the flow of nociceptive impulses from the area of damage to the central nervous system

Limiting the entry of nociceptive impulses into the CNS is achieved by using local anesthetics, which can not only prevent sensitization of nociceptive neurons, but also help normalize microcirculation in the area of damage, reduce inflammatory reactions and improve metabolism. Along with this, local anesthetics, by relaxing the striated muscles, eliminate pathological reflex muscle tension, which is an additional source of pain.

The mechanism of action of local anesthetics is associated with the blocking of Na+ -channels on the membrane of nerve fibers and inhibition of the generation of action potentials.

Agents activating structures of the antinociceptive system

To activate the antinociceptive system, which controls the conduction of nociceptive impulses in the central nervous system, narcotic analgesics, antidepressants, non-opioid analgesics of central action are used.

Narcotic analgesics are a class of drugs whose mechanism of analgesic action is due to binding to opioid receptors. There are several subtypes of opioid receptors: mu-, kappa-, sigma- and delta-opioid receptors. Depending on the nature of the interaction with opioid receptors, narcotic analgesics are divided into agonists (codeine, morphine, fentanyl), partial agonists (buprenorphine), agonists-antagonists (butorphanol, nalbuphine) and antagonists (naloxone). Agonists, binding to receptors, cause a response characteristic of endogenous ligands. Antagonists, on the contrary, block the action of endogenous ligands. As a rule, narcotic analgesics interact with several types of opioid receptors, acting in relation to some as agonists, in relation to others as partial agonists or antagonists.

In its own way analgesic activity narcotic analgesics are divided into weak (codeine, pentazocine), medium (nalbuphine) and strong (morphine, buprenorphine, fentanyl).

The appointment of narcotic analgesics requires a differentiated approach and is determined by the cause, nature and severity of the pain syndrome. They are generally used as highly effective pain relievers for trauma, surgery, and cancer patients with moderate to severe pain. Along with this, in a number of countries in Western Europe and the United States, strong opioids have been prescribed for the treatment of chronic non-cancer pain for more than 15 years. Opioids began to be used in patients with rheumatoid arthritis, back pain, neuropathic pain. Opioid analgesics began to be prescribed as an alternative to non-narcotic analgesics in case of their ineffectiveness or if patients have contraindications for their use (nephro- and gastrotoxicity of non-steroidal anti-inflammatory drugs, hepatotoxicity of paracetamol). Long-acting narcotic analgesics (MCT-Continus) have appeared in clinical practice, which can be administered without a syringe in the form of suppositories, buccal, sublingual (buprenorphine) or transdermal forms (buprenorphine, fentanyl). However, in the treatment of chronic pain with opioids, there is always a risk of developing complications in the form of addiction, physical dependence, tolerance, respiratory depression, and constipation.

For the treatment of moderate to severe pain, including in non-cancer patients, a centrally acting analgesic, tramadol, is used. Tramadol is an opioid receptor agonist that simultaneously inhibits the reuptake of serotonin and norepinephrine in nerve synapses. An important advantage of tramadol over other strong opioid analgesics is its extremely low potential for the development of tolerance and physical dependence, therefore it does not apply to narcotic drugs and is prescribed on a prescription form for potent substances. This drug has found its application in the treatment of pain in oncology, surgery, traumatology, rheumatology, neurology, cardiology. Recently, of particular interest are the results of the combined use of tramadol with non-narcotic analgesics, which provide not only a high analgesic effect, but also a decrease in side effects from NSAID monotherapy. So, to enhance the analgesic effect, a combination of Nurofen with paracetamol and tramadol is possible for two days.

Antidepressants are widely used in the treatment of various chronic pain syndromes, and especially in oncology, neurology and rheumatology. In the treatment of pain syndromes, drugs are mainly used, the mechanism of action of which is associated with the blockade of the neuronal reuptake of monoamines (serotonin and norepinephrine) in the central nervous system. The greatest analgesic effect was observed in amitriptyline. Analgesic properties have also been described for imipramine, doxepin, duloxetine, trazodone, maprotiline and paroxetine. The development of an analgesic effect in the treatment of patients with pain syndromes with antidepressants is associated with an increase in the tonic activity of the antinociceptive system. Antidepressants are auxiliary analgesics and are usually used in combination with traditional painkillers. Anxiety-depressive disorders associated with chronic pain syndromes exacerbate the pain perception and suffering of patients, which is the basis for prescribing antidepressants. In addition to their own analgesic effect, antidepressants potentiate the effect of narcotic analgesics, enhancing their relationship with opioid receptors.

Means for eliminating ectopic impulses in peripheral nerves and inhibiting the excitability of central nociceptive neurons

Anticonvulsants or anticonvulsants are coming to the fore for the treatment of neurogenic pain syndromes. Anticonvulsants effectively block ectopic impulses in peripheral nerves and pathological hyperactivity in central nociceptive neurons. The mechanism of action of anticonvulsants is associated with the blockade of NA+ - channels, CA 2+ -channels, changes in GABA metabolism and decreased secretion of glutamate. Many of the anticonvulsant drugs combine two or even three of the above methods of influencing the excitability of the neuronal membranes of hyperactivated neurons. The analgesic effect of anticonvulsants that predominantly block voltage-dependent sodium channels (phenytonin, carbamazepine, oxcarbazepine) is achieved by inhibition of ectopic discharges that occur in the damaged nerve and a decrease in the excitability of central neurons.

Pain relievers for muscle tension

Reduction of muscle tension can also be achieved with central muscle relaxants (benzodiazepines, baclofen, tolperisone, tizanidine) or by local injection of botulinum toxin type A into the muscle.

Baclofen is a GABA agonist AT -receptors and, due to inhibition at the spinal level of intercalary neurons, has a pronounced antispastic and analgesic effect. Baclofen is used for painful muscle spasms in patients with spinal cord and brain lesions.

Tolperisone is used as a centrally acting muscle relaxant. The drug, due to the membrane-stabilizing effect and suppression of the secretion of glutamic acid from the central terminals of the primary afferent fibers, reduces the frequency of action potentials in sensitized nociceptors and inhibits increased polysynaptic reflex activity in the spinal cord. This action of tolperisone provides an effective break in the chain of pathological events: damage - pain - muscle spasm - pain. The drug is indicated for spastic syndrome caused by damage to the descending motor pathways of the brain and spinal cord, as well as for the treatment of musculoskeletal pain syndromes.

The muscle relaxant and analgesic effect of tizanidine is due to the suppression of the release of excitatory amino acids in spinal cord neurons due to the activation of presynaptic α by tizanidine. 2 -adrenergic receptors. In addition to muscle-spastic conditions caused by damage to the spinal cord and brain, tizanidine is also used for painful muscle tension in patients with pathology of the musculoskeletal system.

In the treatment of myofascial pain syndromes, local injection of botulinum toxin type A, which blocks the release of acetylcholine in the neuromuscular synapse, into the area of painful muscle indurations is also used. The resulting muscle relaxation can provide a long-term (up to 3-6 months) analgesic effect. Currently, botulinum toxin type A is used to treat myofascial pain in vertebrogenic pathology of the cervical, thoracic and lumbar, with pain dysfunction of the temporomandibular joint, with chronic tension headache.

Normalization of the psychological state of the patient

For the treatment of psychological problems in patients with chronic pain, it is necessary to use an integrated approach that combines the methods of psychotherapy, reflexology, exercise therapy and pharmacotherapy. The strategy of psychotherapy should be directed:

to eliminate internal psychological conflict;
to mobilize the natural capabilities of a person that can change the already habitual "pain behavior";
to educate patients on self-regulation methods that reduce the intensity of pain.

Depending on the nature of psychopathological symptoms, the severity of the motivations and performance of a patient with chronic pain, various psychotherapeutic techniques can be used - supportive psychotherapy, suggestive techniques (hypnosis, autogenic relaxation, meditation), dynamic psychotherapy, group psychotherapy, behavioral therapy, biofeedback.

Reflexotherapy methods provide an analgesic effect by activating the structures of the antinociceptive system, reducing psychological stress and muscle tone.

Physiotherapy helps to increase the level of physical activity of the patient, contributes to the normalization of his psychological background and social adaptation.

The prescription of drugs in patients with psychogenic pain syndromes should be built in accordance with the structure of the psychopathological symptom complex. With the dominance of depressive manifestations, antidepressants are used that have both antidepressant and analgesic effects - amitriptyline, paroxetine, fluoxetine. In the presence of anxiety-phobic disorders, benzodiazepine drugs (alprazolam, clonazepam) and antidepressants with a sedative and anti-anxiety effect (amitriptyline, mianserin) are prescribed. In case of predominance of hypochondriacal symptoms, small antipsychotics (thioridazine, frenolon) are used.

Principles of treatment of pain syndromes

V.V. Alekseev Department of Nervous Diseases MMA them. THEM. Sechenov, Moscow

Under normal conditions, pain is a protective biological phenomenon and mobilizes all the functional systems necessary for the survival of the body, allowing to overcome the harmful effects that provoked it, or to avoid them. About 90% of all diseases are associated with pain. According to various researchers, from 7 to 64% of the population periodically experience pain, and from 7 to 45% suffer from recurrent or chronic pain.

Therapy of pain syndromes involves determining and eliminating the source or cause of pain, determining the degree of involvement of various parts of the nervous system in the formation pain sensation and the removal or suppression of the pain itself. The initial, or most peripheral, link in the pain perception system is the irritation of pain receptors (nociceptors), which are free nerve endings of afferent fibers.

After a very complex processing of pain afferentation in the segmental apparatus of the spinal cord, where it is affected by excitatory and inhibitory influences emanating from the peripheral and central parts of the nervous system, nociceptive impulses are transmitted through interneurons to the cells of the anterior and lateral horns, causing reflex motor and vegetative reactions. Another part of the impulses excites neurons whose axons form ascending pathways.

Nociceptive afferentation is sent to the brain along the spinothalamic, spino-reticular, and spinomesencephalic pathways. The entrance gate and relay center for all afferent impulses coming from the underlying sections to the cerebral cortex is the visual tubercle. It has been shown that the reticular thalamic nuclei can play a modulating inhibitory role in the thalamic nociceptive system. At the level of the hypothalamus and formations of the limbic complex, the formation of emotional and behavioral reactions, vegetative and endocrine changes that accompany pain occurs. The final analysis of incoming nociceptive information is carried out by the cortex of the parietal, frontal and temporal lobes of the brain.

Afferent information comes to the somatosensory cortex from the ipsilateral parts of the thalamus. Corticofugal fibers go from the post-central sections of the parietal cortex to the same nuclei of the thalamus opticus and are partly included in the

becoming corticobulbar and corticospinal descending tracts. At the level of the somatosensory cortex, spatiotemporal analysis of pain information is carried out. Corticofugal fibers from the frontal cortex are sent both to the same thalamic structures and to the neurons of the reticular formation of the trunk, formations of the limbic system (cingulate gyrus, hippocampus, fornix, septum, entorhinal cortex) and the hypothalamus. Thus, the frontal regions of the cortex, along with providing cognitive and behavioral components of the integrative response to pain, are involved in the formation of a motivational-affective assessment of pain sensation. The temporal regions of the cortex play an important role in the formation of sensory memory, which allows the brain to evaluate the current pain sensation, comparing it with the previous ones. Thus, the state of the suprasegmental structures of the CNS - the cortex, the limbic system, the stem-diencephalic formations that form the motivational-affective and cognitive components of pain behavior, also actively influences the conduction of pain afferentation.

The descending inhibitory cerebrospinal control over the conduction of pain impulses is a function of the antinociceptive system, carried out by the structures of the cerebral cortex, the diencephalic level, the periventricular and periaqueductal gray matter, rich in enkephalin and opiate neurons, some nuclei of the reticular formation of the brain stem, the main of which is big core seam, where the main neurotransmitter is serotonin. The axons of the neurons of this nucleus are sent down the dorsolateral funiculus of the spinal cord, ending in the superficial layers of the posterior horn. Some of them, like most of the axons from the reticular formation, are noradrenergic. The participation of serotonin and norepinephrine in the functioning of the antinociceptive system explains the pain relief caused by tricyclic antidepressants, the main property of which is the suppression of reuptake in the serotonergic and norepinephrine synapses and, thereby, an increase in the descending inhibitory effect on the neurons of the dorsal horn of the spinal cord.

Importance in the functioning of the antinociceptive system have opiates. Opiate receptors are located at the ends of C-fibers in the posterior horn of the spinal cord, in descending inhibitory pathways from the brain to the spinal cord, and in areas of the brain that transmit pain signals.

Type C fibers can contact inhibitory enkephalinergic interneurons that inhibit the conduction of pain impulses in the posterior horns and nucleus of the spinal cord. trigeminal nerve. In this case, enkephalin can act by inhibiting the activity of spinothalamic neurons and inhibiting the release of excitatory neurotransmitters in the posterior horns from the central axon terminals of USC neurons. Inhibition of the release of excitatory transmitters is also provided by other pain inhibitors - these are GABA and glycine, found in intercalary neurons spinal cord. These endogenous substances modulate CNS activity and inhibit pain signal transmission. Serotonin and norepinephrine also inhibit the pain response as part of the descending pathway from the brain to the spinal cord that controls the pain mechanism.

Thus, under normal conditions, there is a harmonious relationship between in-

the intensity of the stimulus and the response to it at all levels of the organization of the pain system, which does not allow you to experience pain. However, long-term repeated damaging effects often lead to a change in the functional state (increased reactivity) of the pain system, which gives rise to its pathophysiological changes. From this point of view, there are nociceptive, neuropathic and psychogenic pain.

Nociceptive pain occurs with any tissue injury that causes excitation of peripheral pain receptors and specific somatic or visceral afferent fibers. Nociceptive pain is usually transient or acute - the painful stimulus is obvious, the pain is usually clearly localized and well described by patients. The exception is visceral pain and referred pain. Nociceptive pain is characterized by rapid regression after the appointment of a short course of painkillers, including narcotic analgesics.

Neuropathic pain is caused by damage or changes in the state of the somatosensory (peripheral and/or central parts) system. Neuropathic pain can develop and persist in the absence of an obvious primary pain stimulus, manifests itself in the form of a series of characteristic features, often poorly localized and accompanied by various disorders of surface sensitivity: hyperalgesia (intense pain with mild nociceptive irritation of the primary injury zone or neighboring and even distant zones); allodynia (the occurrence of pain when exposed to non-painful stimuli of various modalities); hyperpathy (pronounced reaction to repeated pain effects with the preservation of the sensation of severe pain after the cessation of pain stimulation); pain anesthesia (feeling of pain in areas devoid of pain sensitivity). Neuropathic pain is less susceptible to morphine and other opiates at conventional analgesic doses, which indicates a difference in its mechanisms from nociceptive pain.

Neuropathic pain can be spontaneous or induced. Spontaneous pain may have a burning quality, usually found on the skin surface and reflecting activation of peripheral C-nociceptors. Such pain can also be acute when it is caused by excitation of low-myelinated A-delta nociceptive skin afferents. Shooting pains, similar to an electrical discharge, radiating to a segment of a limb or face, are usually the result of ectopic generation of impulses along the paths of low-myelinated C-fibers of muscle afferents that respond to damaging mechanical and chemical stimuli. The activity of this type of afferent fibers is perceived as "cramp-like pain".

In relation to the degree of involvement of the sympathetic nervous system, spontaneous pain can be divided into sympathetically independent and sympathetically conditioned. Sympathetically independent pain is associated with the activation of primary nociceptors as a result of damage to the peripheral nerve and disappears or significantly regresses after local anesthetic blockade of the damaged peripheral nerve or the affected area of the skin. Pain syndrome of this type is associated with the release of inflammatory mediators, this is its similarity with the pain syndrome that develops during inflammation in the absence of damage to the peripheral nerve. Sympathetically independent pain, as a rule, has a sharp, shooting character.

Induced neuropathic pain is usually accompanied by allodynia and hyperalgesia. Allodynia is caused by activation of low-threshold myelinated Ap fibers in the central nervous system or by a decrease in the sensitivity threshold of nociceptive endings in the periphery. Hyperalgesia is usually caused by mechanical and thermal stimuli.

Psychogenic pain occurs in the absence of any organic lesion that would explain the severity of the pain and associated functional disorders. The question of the existence of pain of exclusively psychogenic origin is debatable, however, certain features of the patient's personality can influence the formation of pain sensation. Psychogenic pain may be one of the many disorders that are characteristic of somatoform disorders. Any chronic illness or malaise, accompanied by pain, affects the emotions and behavior of the individual. Pain often leads to anxiety and tension, which themselves increase the perception of pain. Psychophysiological (psychosomatic) mechanisms, acting through the corticofugal systems, change the state of internal organs, striated and smooth muscles, stimulate the release of algogenic substances and the activation of nociceptors. The resulting pain, in turn, exacerbates emotional disturbances, thus completing a vicious circle.

Information about the drug

INDICATIONS

Short-term treatment of acute conditions in articular syndrome with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout; acute pain syndrome with neuritis, neuralgia, sciatica (including degenerative diseases of the spine).

DOSING MODE

The drug is prescribed 1 injection per day daily or every other day. Make no more than 3 injections per week. If necessary, carry out

AMBENE (Germany, ratiopharm) Double ampoules, ready-made syringes

For repeated courses of treatment, the interval between them should be at least several weeks. Injections of the drug are made deep in / m, slowly; the patient should be in a horizontal position.

Sections: Pharmacological action, Pharmacokinetics, Preparation rules injection solution, Contraindications, Side effects, Pregnancy and lactation, special instructions, Overdose, Drug interaction - see the instructions for use of the drug.

physical illness, depression often also develops. The most rare form of pain in mental illness is its hallucinatory form, which is observed in patients with endogenous psychoses. The psychological mechanisms of pain also include cognitive mechanisms that link pain with conditional social benefits, receiving emotional support, attention, and love.

The classification of the temporal aspect of pain distinguishes between transient, acute and chronic pain.

Transient pain is provoked by the activation of nociceptive transducer receptors in the skin or other tissues of the body in the absence of significant tissue damage. The function of such pain is determined by the rate of occurrence after stimulation and the rate of elimination, which indicates that there is no danger of a damaging effect on the body. In clinical practice, for example, transient pain is observed during intramuscular or intravenous injection. It is assumed that transient pain exists to protect a person from the threat of physical damage by environmental factors in the form of a kind of learning or pain experience.

Acute pain is divided into superficial, deep, visceral and reflected. These types of acute pain differ in subjective sensations, localization, pathogenesis and causes.

Chronic pain in neurological practice is a much more urgent condition. The International Association for the Study of Pain defines chronic pain as "...pain that continues beyond the normal healing period." In practice, this can take several weeks or more than six months. Chronic pain can also include recurring pain conditions (neuralgia, headaches of various origins, etc.). The point, however, is not so much in temporal differences, but in qualitatively different neurophysiological, psychological and clinical features. The main point is that acute pain is always a symptom, while chronic pain can become essentially a disease in itself. It is clear that the therapeutic tactics in the elimination of acute and chronic pain has significant features. Chronic pain in its pathophysiological basis may have a pathological process in the somatic sphere and / or primary or secondary dysfunction of the peripheral or central nervous system, it can also be caused by psychological factors. It is important to clearly understand that untimely and inadequate treatment of acute pain can become the basis for its transformation into chronic pain.

Nociceptive afferentation exceeding the physiological threshold is accompanied by the release of algogenic compounds (hydrogen and potassium ions, serotonin, histamine, prostaglandins, bradykinin, substance P) into the intercellular fluid surrounding the nociceptors. These substances play a key role in the formation of pain caused by damage, ischemia and inflammation. In addition to the direct excitatory effect on the membranes of nociceptors, there is an indirect mechanism associated with impaired local microcirculation. Increased capillary permeability promotes extravasation of such active substances as plasma kinins and serotonin. This, in turn, disrupts the physiological and chemical environment around the nociceptors and increases their excitation. The continued release of inflammatory mediators can cause a prolonged impulse with the development of sensitization of nociceptive neurons and the formation of "secondary hyperalgesia" of the damaged tissue, contributing to the chronicity of the pathological process.

The mechanisms of pain caused by the inflammatory process are currently being actively studied. It has been shown that any peripheral pain is associated with an increase in the sensitivity of nociceptors. An increase in the sensitivity of the primary nociceptor in the affected peripheral tissue leads to an increase in the activity of neurons that send impulses to the spinal cord and CNS, however, it must be emphasized that spontaneous electrical activity can be generated in the focus of inflammation, causing a persistent pain syndrome. Pro-inflammatory components such as bradykines, histamine, neurokinins, nitric oxide, which are usually found in the focus of inflammation, are such a powerful inducer of pain sensitivity. Prostaglandins themselves are not pain moderators, they only increase the sensitivity of nociceptors to various stimuli, and their accumulation correlates with the development of inflammation intensity and hyperalgesia. Prostaglandins, as it were, mediate the involvement of "sleeping" nociceptors in the formation of secondary inflammatory hyperalgesia and peripheral sensitization. Therefore, based on general principles pain therapy, first of all, the effect is on its source, receptors and peripheral

fibers, and then to the posterior horns of the spinal cord, the conduction systems of pain, the motivational-affective sphere and the regulation of behavior.

Treatment of pain involves the use of several main classes of drugs: non-steroidal or steroidal anti-inflammatory drugs, simple and combined analgesics.

One of the drugs that optimally meet these requirements is Ambene (ratiopharm). The drug is intended for intramuscular injection and is available in ready-made syringes. It consists of: dexamethasone (inhibition of the production of cytokines, prostaglandins, leukotrienes, accumulation of neutrophils), NSAIDs - phenylbutazone (prolonged analgesic and anti-inflammatory effect), sodium salicylamidoacetate (analgesic effect and improvement of the solubility of the drug), cyanocobalamin (cell regeneration, remyelination of nerve fibers), lidocaine (analgesic effect). Ambene injections are prescribed every other day, no more than three injections per week. No side effects were noted.

These drugs and methods can be used separately or, more often, combined, depending on the specific clinical situation. A separate aspect of the problem of pain is the tactics of managing patients. The experience available today has proved the need for examination and treatment of patients with acute and especially chronic pain in specialized centers of inpatient or outpatient type with participation in their diagnosis and treatment of various specialists - neurologists, therapists, anesthesiologists, psychologists, clinical electrophysiologists, physiotherapists, etc.

In conclusion, it should be noted that the general principles of pain treatment provide for a clinical assessment of the state of the neurophysiological and psychological components of the nociceptive and antinociceptive systems and the impact on all levels of organization of this system.

Therapy of pain syndromes involves determining and eliminating the source or cause that caused pain, determining the degree of involvement of various parts of the nervous system in the formation of pain and removing or suppressing the pain itself. The initial, or most peripheral, link in the pain perception system is the stimulation of pain receptors (nociceptors), which are free nerve endings of afferent fibers.

The first central link that perceives multimodal afferent information is the neuronal system of the dorsal horn of the spinal cord. It is a cytoarchitectonically very complex structure, which in functional terms can be considered as a kind of primary integrative center of sensory information.
After a very complex processing of pain afferentation in the segmental apparatus of the spinal cord, where it is affected by excitatory and inhibitory influences emanating from the peripheral and central parts of the nervous system, nociceptive impulses are transmitted through interneurons to the cells of the anterior and lateral horns, causing reflex motor and autonomic reactions. Another part of the impulses excites neurons whose axons form ascending pathways.
Nociceptive afferentation is sent to the brain along the spinothalamic, spinoreticular, and spinomesencephalic pathways. The entrance gate and relay center for all afferent impulses coming from the underlying sections to the cerebral cortex is the visual tubercle. It has been shown that the reticular thalamic nuclei can play a modulating inhibitory role in the thalamic nociceptive system. At the level of the hypothalamus and formations of the limbic complex, the formation of emotional and behavioral reactions, vegetative and endocrine changes that accompany pain occurs. The final analysis of incoming nociceptive information is carried out by the cortex of the parietal, frontal and temporal lobes of the brain.

Afferent information comes to the somatosensory cortex from the ipsilateral parts of the thalamus. Corticofugal fibers run from the postcentral parts of the parietal cortex to the same nuclei of the thalamus opticus and are partly included in the corticobulbar and corticospinal descending tracts. At the level of the somatosensory cortex, spatiotemporal analysis of pain information is carried out. Corticofugal fibers from the frontal cortex are sent both to the same thalamic structures and to the neurons of the reticular formation of the trunk, formations of the limbic system (cingulate gyrus, hippocampus, fornix, septum, entorhinal cortex) and the hypothalamus. Thus, the frontal regions of the cortex, along with providing cognitive and behavioral components of the integrative response to pain, are involved in the formation of a motivational-affective assessment of pain sensation. The temporal regions of the cortex play an important role in the formation of sensory memory, which allows the brain to evaluate the current pain sensation, comparing it with the previous ones. Thus, the state of the suprasegmental structures of the CNS - the cortex, the limbic system, the stem-diencephalic formations that form the motivational-affective and cognitive components of pain behavior, also actively influences the conduction of pain afferentation.
The descending inhibitory cerebrospinal control over the conduction of pain impulses is a function of the antinociceptive system, carried out by the structures of the cerebral cortex, the diencephalic level, the periventricular and periaqueductal gray matter, rich in enkephalin and opiate neurons, some nuclei of the reticular formation of the brain stem, the main of which is the large raphe nucleus, where the main the neurotransmitter is serotonin. The axons of the neurons of this nucleus are sent down the dorsolateral funiculus of the spinal cord, ending in the superficial layers of the posterior horn. Some of them, like most of the axons from the reticular formation, are noradrenergic. The participation of serotonin and norepinephrine in the functioning of the antinociceptive system explains the pain relief caused by tricyclic antidepressants, the main property of which is the suppression of reuptake in serotonergic and norepinephrine synapses and, thereby, an increase in the descending inhibitory effect on the neurons of the dorsal horn of the spinal cord.
Opiates play an important role in the functioning of the antinociceptive system. Opiate receptors are located at C-fiber terminals in the dorsal horn of the spinal cord, in descending inhibitory pathways from the brain to the spinal cord, and in areas of the brain that transmit pain signals.

Type C fibers can contact inhibitory enkephalinergic interneurons that inhibit the conduction of pain impulses in the posterior horns and the nucleus of the spinal tract of the trigeminal nerve. In this case, enkephalin can act by inhibiting the activity of spinothalamic neurons and inhibiting the release of excitatory neurotransmitters in the posterior horns from the central axon terminals of USC neurons. Inhibition of the release of excitatory transmitters is also provided by other pain inhibitors - these are GABA and glycine found in the interneurons of the spinal cord. These endogenous substances modulate CNS activity and inhibit pain signal transmission. Serotonin and norepinephrine also inhibit the pain response as part of the descending pathway from the brain to the spinal cord that controls the pain mechanism.
Thus, under normal conditions, there is a harmonious relationship between the intensity of the stimulus and the response to it at all levels of the organization of the pain system, which does not allow one to experience pain. However, long-term repeated damaging effects often lead to a change in the functional state (increased reactivity) of the pain system, which gives rise to its pathophysiological changes. From this point of view, there are nociceptive, neuropathic and psychogenic pain.
Nociceptive pain occurs with any tissue injury that causes excitation of peripheral pain receptors and specific somatic or visceral afferent fibers. Nociceptive pain is usually transient or acute - the painful stimulus is obvious, the pain is usually clearly localized and well described by patients. The exception is visceral pain and referred pain. Nociceptive pain is characterized by rapid regression after the appointment of a short course of painkillers, including narcotic analgesics.
Neuropathic pain is caused by damage or changes in the state of the somatosensory (peripheral and / or central parts) system. Neuropathic pain can develop and persist in the absence of an obvious primary pain stimulus, manifests itself in the form of a number of characteristic signs, is often poorly localized and is accompanied by various disorders of surface sensitivity: hyperalgesia (intense pain with mild nociceptive irritation of the primary injury zone or neighboring and even distant zones); allodynia (the occurrence of pain when exposed to non-painful stimuli of various modalities); hyperpathy (pronounced reaction to repeated pain effects with the preservation of the sensation of severe pain after the cessation of pain stimulation); pain anesthesia (feeling of pain in areas devoid of pain sensitivity). Neuropathic pain is less susceptible to morphine and other opiates at conventional analgesic doses, which indicates a difference in its mechanisms from nociceptive pain.
Neuropathic pain can be spontaneous or induced. Spontaneous pain may have a burning quality, usually found on the skin surface and reflecting activation of peripheral C-nociceptors. Such pain can also be acute when it is caused by stimulation of low-myelinated A-delta nociceptive skin afferents. Shooting pains, similar to an electrical discharge, radiating to a segment of a limb or face, are usually the result of ectopic generation of impulses along the paths of undermyelinated C-fibers of muscle afferents that respond to damaging mechanical and chemical stimuli. The activity of this type of afferent fibers is perceived as "cramp-like pain".
In relation to the degree of involvement of the sympathetic nervous system, spontaneous pain can be divided into sympathetically independent and sympathetically conditioned. Sympathetically independent pain is associated with activation of primary nociceptors as a result of damage to the peripheral nerve and disappears or significantly regresses after local anesthetic blockade of the damaged peripheral nerve or the affected area of the skin. Pain syndrome of this type is associated with the release of inflammatory mediators, this is its similarity with the pain syndrome that develops during inflammation in the absence of damage to the peripheral nerve. Sympathetically independent pain, as a rule, has a sharp, shooting character.

Induced neuropathic pain is usually accompanied by allodynia and hyperalgesia. Allodynia is caused by activation of low-threshold myelinated Ab fibers in the central nervous system or by a decrease in the sensitivity threshold of nociceptive endings in the periphery. Hyperalgesia is usually caused by mechanical and thermal stimuli.

Psychogenic pain occurs in the absence of any organic lesion that would explain the severity of the pain and associated functional impairment. The question of the existence of pain of exclusively psychogenic origin is debatable, however, certain features of the patient's personality can influence the formation of pain sensation. Psychogenic pain may be one of the many disorders that are characteristic of somatoform disorders. Any chronic disease or ailment accompanied by pain affects the emotions and behavior of the individual. Pain often leads to anxiety and tension, which themselves increase the perception of pain. Psychophysiological (psychosomatic) mechanisms, acting through the corticofugal systems, change the state of internal organs, striated and smooth muscles, stimulate the release of algogenic substances and the activation of nociceptors. The resulting pain, in turn, exacerbates emotional disturbances, thus completing a vicious circle.

Among other forms of mental disorders, depression is most closely associated with chronic pain. There are various options for the temporal relationship of these disorders - they can occur simultaneously or one ahead of the manifestations of the other. In these cases, depression is more often not endogenous, but psychogenic. The relationship between pain and depression is quite complex. Patients with clinically significant depression have a reduced pain threshold, and pain is considered a common complaint in patients with primary depression, which may occur in the form of "masked" depression. Patients with pain associated with a chronic somatic disease often also develop depression. The most rare form of pain in mental illness is its hallucinatory form, which is observed in patients with endogenous psychoses. The psychological mechanisms of pain also include cognitive mechanisms that link pain with conditional social benefits, receiving emotional support, attention, and love.

The classification of the temporal aspect of pain distinguishes between transient, acute and chronic pain.

Acute pain is a necessary biological adaptive signal about a possible (in the case of pain experience), incipient or already occurring damage. The development of acute pain is associated, as a rule, with well-defined pain irritations of superficial or deep tissues and internal organs or a violation of the function of smooth muscles of internal organs without tissue damage. The duration of acute pain is limited by the time of repair of damaged tissues or the duration of smooth muscle dysfunction. Neurological causes of acute pain can be traumatic, infectious, dysmetabolic, inflammatory and other damage to the peripheral and central nervous system, meninges, short neural or muscle syndromes.
Acute pain is divided into superficial, deep, visceral and reflected. These types of acute pain differ in subjective sensations, localization, pathogenesis and causes.
Chronic pain in neurological practice is a much more relevant condition. The International Association for the Study of Pain defines chronic pain as "...pain that continues beyond the normal healing period." In practice, this can take several weeks or more than six months. Chronic pain can also include recurring pain conditions (neuralgia, headaches of various origins, etc.). The point, however, is not so much in temporal differences, but in qualitatively different neurophysiological, psychological and clinical features. The main point is that acute pain is always a symptom, while chronic pain can become essentially a disease in itself. It is clear that the therapeutic tactics in the elimination of acute and chronic pain has significant features. Chronic pain in its pathophysiological basis may have a pathological process in the somatic sphere and / or primary or secondary dysfunction of the peripheral or central nervous system, it can also be caused by psychological factors. It is important to clearly understand that untimely and inadequate treatment of acute pain can become the basis for its transformation into chronic pain.
Nociceptive afferentation exceeding the physiological threshold is accompanied by the release of algogenic compounds (hydrogen and potassium ions, serotonin, histamine, prostaglandins, bradykinin, substance P) into the intercellular fluid surrounding the nociceptors. These substances play a key role in the formation of pain caused by damage, ischemia and inflammation. In addition to the direct excitatory effect on the membranes of nociceptors, there is an indirect mechanism associated with impaired local microcirculation. Increased capillary permeability promotes extravasation of active substances such as plasma kinins and serotonin. This, in turn, disrupts the physiological and chemical environment around the nociceptors and increases their excitation. The continued release of inflammatory mediators can cause prolonged impulsation with the development of sensitization of nociceptive neurons and the formation of "secondary hyperalgesia" of the damaged tissue, contributing to the chronicity of the pathological process.
The mechanisms of pain caused by the inflammatory process are currently being actively studied. It has been shown that any peripheral pain is associated with an increase in the sensitivity of nociceptors. An increase in the sensitivity of the primary nociceptor in the affected peripheral tissue leads to an increase in the activity of neurons that send impulses to the spinal cord and CNS, however, it must be emphasized that spontaneous electrical activity can be generated in the focus of inflammation, causing a persistent pain syndrome. Pro-inflammatory components such as bradykines, histamine, neurokinins, nitric oxide, which are usually found in the focus of inflammation, are such a powerful inducer of pain sensitivity. Prostaglandins themselves are not pain moderators, they only increase the sensitivity of nociceptors to various stimuli, and their accumulation correlates with the development of inflammation intensity and hyperalgesia. Prostaglandins, as it were, mediate the involvement of "sleeping" nociceptors in the formation of secondary inflammatory hyperalgesia and peripheral sensitization. Therefore, based on the general principles of pain therapy, first of all, the effect is on its source, receptors and peripheral fibers, and then on the posterior horns of the spinal cord, the pain conducting systems, the motivational-affective sphere and the regulation of behavior.
Treatment of pain involves the use of several main classes of drugs: non-steroidal or steroidal anti-inflammatory drugs, simple and combined analgesics.
One of the drugs that optimally meet these requirements is Ambene (ratiopharm). The drug is intended for intramuscular injection and is available in ready-made syringes. It consists of: dexamethasone (inhibition of the production of cytokines, prostaglandins, leukotrienes, accumulation of neutrophils), NSAIDs - phenylbutazone (prolonged analgesic and anti-inflammatory effect), sodium salicylamidoacetate (analgesic effect and improvement of the solubility of the drug), cyanocobalamin (cell regeneration, remyelination of nerve fibers) , lidocaine (analgesic effect). Ambene injections are prescribed every other day, no more than three injections per week. No side effects were noted.

In the treatment of chronic pain syndromes, first-line drugs are tricyclic antidepressants, among which both non-selective and selective serotonin and norepinephrine reuptake inhibitors are used. The next line of drugs are anticonvulsants.
These drugs and methods can be used separately or, more often, in combination, depending on the specific clinical situation. A separate aspect of the problem of pain is the tactics of managing patients. The experience available today has proved the need for examination and treatment of patients with acute and especially chronic pain in specialized centers of inpatient or outpatient type with participation in their diagnosis and treatment of various specialists - neurologists, therapists, anesthesiologists, psychologists, clinical electrophysiologists, physiotherapists, etc.

The general principles of pain treatment provide for a clinical assessment of the state of the neurophysiological and psychological components of the nociceptive and antinociceptive systems and the impact on all levels of organization of this system.

^ ACUTE PAIN SYNDROME

Acute pain is one of the most common reasons for seeking emergency care worldwide. According to CordeLL W. H. et al. (2002), pain is the reason for the appeal of patients in 52% of all cases of emergency medical care. In Russia, according to the National Scientific and Practical Society for Emergency Medicine (NNSPOSMP), over the past three years, the total number of emergency calls (AMS) due to acute or chronic pain has increased by almost 25%. According to available data, in 20-25% of cases, the cause of emergency treatment is severe pain, and in 10-15% - pain of moderate intensity.

At the same time, not all patients with acute pain receive adequate pain relief. So, according to a study by McLean S. A. et al. (2002), according to patients, only 21% of patients received full-fledged care from all those who underwent urgent anesthesia. Wilson J. E. and Pendleton J. M. (1989), in a retrospective study, found that out of 198 patients who sought help for acute pain, only 44% received help in the emergency department. Moreover, 62% of these patients waited for pain relief for more than an hour, and in 32% of cases, pain relief was not effective enough. Thus, in cases where pain relief is carried out as part of emergency or emergency therapy, it is not always adequate. The most likely reasons for this are the use of ineffective and outdated drugs or treatment regimens, the refractoriness of patients who often use analgesics, restrictions in prescribing effective treatment due to the possible development of side effects.

It is known that pain is a complex multilevel phenomenon, including unpleasant sensations and emotions associated with actual or possible tissue damage.

Multifactorial Pain Model:

nociception (irritation of receptors);
pain (integration of nociceptive signals at the level of the spinal cord);
suffering (negative sensation generated in the CNS and modulated by emotional situations such as acute or chronic stress);
pain behavior (motor-motivational response of the body, regulated by all components).
According to the multifactorial model of pain, irritation of pain receptors in the pathological focus (nociception) leads to a number of pathological neurosomatic symptoms and specific behavior in the patient; this allows us to conclude that the patient is in pain. The mechanisms of formation of these neurosomatic symptoms also vary.

Mechanisms of pain formation and its manifestation

Nociceptive pain (activation of pain receptors):

reflected pain;
arthralgia;
myalgia;
myofascial syndrome (trigger points).

Neuropathic pain:

algoneurodystrophy;
tunnel syndrome. Psychogenic pain:
discrepancy between complaints and objective signs of pain;
non-localized nature of pain, its migration;
treatment failure;
numerous crises.

The combination of nociceptive pain with psychogenic:

chronic pain syndromes, including fibromyalgia.

In turn, the emotional reaction of the patient is determined by a combination of factors that ultimately affect the identification of the cause of the development of the pain syndrome: the severity and duration of pain, the temperament and psycho-emotional constitution of the patient, his attitude to the disease and the degree of self-control of pain and disease in general, the quality of social support.

Obviously, the most striking neurovegetative reactions accompany the first acute pain, the total duration of which, according to modern classifications does not exceed 12 weeks. In patients with acute pain, pallor or redness of the skin, cold sweat, pupillary reaction, tachycardia, increased blood pressure, an increase in the frequency and change in the rhythm of breathing, a change in behavior in the form of anxiety or aggression. In chronic pain lasting more than 12 weeks, the above symptoms are usually accompanied by disorders of the asthenoneurotic circle: fatigue, sleep disturbances, loss of appetite, weight loss, decreased libido, constipation, depression.

The intensity of the pain syndrome and the effect of the therapy are evaluated in several ways. The most common of these are the visual analog scale (VAS) and the pain relief analog scale. When applying the VAS, the patient notes the severity of the pain syndrome on a 100 mm scale, where 0 is the absence of pain, 100 is the maximum pain before and 20 minutes after the administration of the drug.

Table Methods for assessing the intensity of pain syndrome
Way	Gradation of pain	When to use
General five-digit scale	0 - no pain 1 - weak (slightly - slightly) 2 - moderate (hurts) 3 - strong (very painful) 4 - unbearable (cannot be tolerated)
Verbal quantitative scale	0... 5... 10 No pain - unbearable pain (what number corresponds to pain?)	When assessed / examined under normal conditions
Visual analog scale (10 cm long line, sliding ruler)	No pain - unbearable pain (mark on the line how bad the pain is)	When assessed / examined under normal conditions. Can be used in children older than 6 years
Unconscious behavioral and psychological parameters (they are not specific, but indicate acute disorder)	Facial grimaces, groans, increased voice, pallor, sweating, lacrimation, pupil dilation, tachycardia, hypertension, respiratory incoordination	When assessing / examining patients in an unconscious state, autistic and critical patients
Assessment of the vital functions of the patient by a doctor	in accordance with general principles. It is important to assess whether the patient can control voluntary bodily functions (coughing, deep breathing, etc.)	Correlate with subjective assessments, should be used in all

To assess the effectiveness of the anesthesia performed, an analog scale for assessing the severity of pain in points is used. 20 minutes after the administration of the drug, the patient is asked the question: “Did the intensity of pain decrease after the administration of the drug compared to the pain before the administration of the drug?” Possible answers are evaluated in points: 0 - the pain did not decrease, 1 - slightly decreased, 2 - decreased, 3 - greatly decreased, 4 - disappeared completely. To assess the effectiveness of pain relief, it is also important to measure the latent time of pain relief - the time from the administration of the drug to the onset of a distinct analgesic effect.

The choice of drugs for prehospital therapy of acute pain is based on the following principles:

the possibility of obtaining a distinct clinical effect with a single application in most patients;
rapid onset of effect;
controllability and reversibility of the effect;
the possibility of parenteral or sublingual administration or, if necessary, obtaining a local effect without the development of a resorptive effect;
the minimum likelihood of developing an undesirable effect or adverse interaction with other drugs, both prescribed simultaneously and taken by patients on their own or as prescribed by a doctor;
economic efficiency, taking into account hospitalizations, repeated calls, including specialized teams.

Thus, in order to select the optimal anesthetic for use at the prehospital stage, it is necessary to know the main pharmacological parameters of the drug: the strength of anesthesia, the main mechanism of action (the level of influence from the standpoint of a multifactorial pain model), the speed of the effect, the possibility of various routes of administration, the main metabolic pathways and options undesirable pharmacological interaction, a list of possible side effects.

Among non-narcotic painkillers, several drugs meet the above requirements in modern medical practice, each of which has its own pharmacological and economic parameters.

Table Prehospital safety of various NSAIDs
Adverse events	Diclofenac, n = 153	Ketorolac, n = 318	Lornoxicam, n = 95
General
Flatulence
Diarrhea		1
Vomit		1
Anorexia
Nausea	1
Dizziness	1	2
Headache			1
Drowsiness		1	1
Discomfort in the epigastrium	1	3
Total	3 (2%)	8 (2,5%)	2 (2,1%)
Local
Pain at the injection site	12	5	1
Infiltration at the injection site
Necrosis at the injection site	1
Total	13 (8,5%)	5 (1,6%)	1 (1%)

Metamizole sodium (analgin, baralgin) is used in practical medicine since 1922, has central and peripheral analgesic, antipyretic, anti-inflammatory and antispasmodic effects. It is known that metamizole inhibits the synthesis of bradykinins and prostaglandins, prevents the conduction of pain extero- and proprioceptive impulses along the CNS pathways, increases the excitability threshold of thalamic centers of pain sensitivity, and increases heat transfer. Metamizole is used for pain of various origins: headache, neuralgia and musculoskeletal pain, renal colic and febrile conditions. Enter intravenously slowly or deeply intramuscularly, the maximum single dose is 1000 mg, the maximum daily dose is 2000 mg. Of the side effects, leukopenia, agranulocytosis, allergic reactions are the most common, and post-infectious infiltrates are possible with intramuscular administration. Metamizole is contraindicated in patients with severe violation parenchymal organs, impaired hematopoiesis, during pregnancy and lactation, children of the first year of life, patients with a history of hypersensitivity reactions to metamizole.

Despite the fact that frequent or continuous use of metamizole is associated with a high risk of severe side effects, the drug has traditionally remained the main tool for urgent pain relief in Russia. It has been established that in Russia, up to 3-5 liters of dipyrone are consumed for 1000 calls to the ambulance crews. Metamizole is used as an analgesic in Austria, Belgium, France, Germany, Italy, the Netherlands, Spain, Switzerland, South Africa, Latin America, Israel and India. At the same time, 34 countries of the world completely stopped or partially restricted the sale of this drug, and in the USA, Norway, Great Britain, the Netherlands, and Sweden, its use was banned back in the mid-70s. The reason for such a radical ban is the impossibility of assessing the uncontrolled use of the drug by the population, although health authorities do not dispute the high efficacy and sufficient safety of metamizole in rare or single appointments in patients who have not experienced hypersensitivity reactions to the drug. In Russia, metamizole is included in the List of medicines approved for medical use annex to the order of the Ministry of Health of the USSR No. 155 dated February 28, 1972, since 2000 its use has been limited in children and adolescents under 18 years of age. Thus, the risk of developing side effects of metamizole during prehospital pain therapy is closely related to the study in each case of the pharmacological history of a patient with acute pain syndrome.

For pain of spastic origin, analgesia is often performed using a combination of analgin and antispasmodic. The use of ready-made combined preparations not only simplifies treatment, but also increases the effectiveness of analgesia and the safety of therapy, since each component weakens the side effects of each other, or the side effects of each component depend on its dose. An example of such a combined agent is revalgin: 1 ml of injection contains 500 mg of metamizole sodium, 2 mg of pitophenone hydrochloride, 0.02 mg of fenpiverinium bromide. Indications for the use of Revalgin are spasms of smooth muscles: renal, biliary colic. According to Sanahuja J. et al. (1990), who conducted a comparative double-blind study of 57 patients with renal colic, the combination of metamizole and two antispasmodics (baralgin 5.0 intravenously) had the same effect as diclofenac (75 mg intramuscularly). But, like other drugs with atropine-like activity, the drug is contraindicated in glaucoma and benign prostatic hyperplasia.

Diclofenac sodium (Voltaren, Ortofen), Ketorolac (Ketorol) and Lornoxicam (Xefocam) are part of the group of non-steroidal anti-inflammatory drugs (NSAIDs). All NSAIDs have analgesic, anti-inflammatory, antipyretic and antiaggregatory effects. The drugs act by non-selective inhibition of cyclooxygenase, the main enzyme in the metabolism of arachidonic acid, which is necessary for the synthesis of prostaglandins and mediators of pain and inflammation. According to Kukes VG (1999), in descending order of analgesic action, these drugs can be arranged in the following sequence: ketorolac > lornoxicam > diclofenac > analgin.

Diclofenac, the most widely used NSAID, is recognized as the "gold standard" for efficacy and safety. In addition to the peripheral, it is assumed that the drug has a central mechanism of analgesic action. However, it was found that the new drug - lornoxicam - has a 100 times greater ability to inhibit cyclooxygenase and suppress the synthesis of prostaglandins than diclofenac. Due to the rapid achievement (15 minutes after intravenous administration) of the maximum plasma concentration, lornoxicam demonstrates high efficiency in renal colic, postoperative pain and pain syndrome caused by degenerative-dystrophic diseases of the spine. In the planned treatment of patients with chronic back pain, lornoxicam at a dose of 8 mg per day for 14 days led to pain relief in 80%, not inferior in effectiveness to diclofenac at a dose of 50 mg twice a day.

Of all NSAIDs, ketorolac appears to have the most pronounced effect on pain of various origins. In North America, the UK, some other European countries, and Hong Kong, ketorolac is the only non-steroidal anti-inflammatory drug used for the treatment of pain as a rapid intravenous injection. It has been shown that intramuscular administration of 30 mg of the drug has an effect comparable to the effect of 10-12 mg of morphine or 50 mg of meperidine. With renal colic intravenous administration 30 mg of ketorolac had the same analgesic effect as intravenous administration of 2.5 g of metamizole in combination with antispasmodics, with fewer side effects. The advantage of ketorolac compared to narcotic analgesics is the absence of an effect on respiratory function, sedative and psychomotor action.

Against the background of diclofenac therapy, side effects are rare, headache, allergic reactions, and abdominal pain are more common. Rare cases have been described hemolytic anemia, necrotizing fasciitis and soft tissue necrosis at the site of intramuscular injection of pre-
paratha. Due to the possibility of such complications, it is advisable to generally avoid intramuscular administration of diclofenac.

A common and life-threatening side effect of all non-selective NSAIDs is their ability to cause dyspepsia and acute erosive and ulcerative lesions of the gastric mucosa and duodenum(NSAID-gastropathy). With planned treatment (more than a month), dyspepsia develops in 30-40%, and ulcers or erosions of the stomach - in 10-20% of patients. It is important to remember that the ulcerogenic effect of NSAIDs in sensitive patients develops at any stage of the introduction of drugs into the body. However, according to the severity of the ulcerogenic effect and the associated risk of acute gastrointestinal bleeding, NSAIDs vary: among the drugs considered in this article, the highest risk of gastrointestinal bleeding is associated with ketorolac, and the lowest with diclofenac. It has been proven that the likelihood of developing gastrointestinal bleeding is higher in patients of the so-called risk group.

The main risk factors for the development of NSAID-gastropathy:

peptic ulcer in history;
age over 65;
concomitant use of corticosteroids.

Side effects during planned therapy with lornoxicam occur in 25% of cases, while 16% of patients have complaints from the gastrointestinal tract. Thus, lornoxicam is not worse tolerated than other NSAIDs. Lornoxicam and ketorolac, like aspirin and diclofenac, inhibit platelet function. This undesirable effect of NSAIDs is also a factor contributing to the development of postoperative and gastrointestinal bleeding during treatment. However, in this regard, it is important to remember that the risk of any adverse reactions to NSAID treatment increases dramatically with increasing duration of treatment and in patients with severe comorbidities ( kidney failure, circulatory failure). In patients who are not at special risk, the likelihood and clinical significance of side effects with NSAID pain relief for 1-3 days are small and occur less frequently than with opioids. However, contraindications to the use of lornoxicam and ketorolac include hypersensitivity to aspirin and other NSAIDs, allergies, high risk of gastric bleeding, bleeding disorders, kidney or liver failure, and children's age (under 16 years).

According to the regulatory documents (Appendix 13 to the order of the Ministry of Health of the Russian Federation of March 26, 1999 No. 100 "Indicative list of equipment for an ambulance team"), the minimum list of painkillers for the SMP includes the following drugs:

2.20. Narcotic analgesics:
- morphine (doltard) 1% - 1 ml,
2 ampoules;
- omnopon 1% - 1 ml, 2 ampoules;
- promedol 2% - 1 ml, 2 ampoules;
- fentanyl 0.005% - 2 ml, 2 ampoules.
2.21. Non-narcotic analgesics:
- metamizole sodium (analgin) 50% - 2 ml, 4 ampoules;
- tramadol (tramal) - 1 ml, 2 ampoules (an opioid analgesic with mixed mechanism actions);
- Moradol - 1 ml, 2 ampoules (opioid receptor agonist-antagonist).
Metamizole sodium (baralgin) is also listed in the article.
2.27. Antispasmodics:
- aminophylline (eufillin) 2.4% - 10 ml, 2 ampoules;
- bendazol (dibazol, glyofen) 1% - 5 ml, 5 ampoules;
- drotaverine (no-shpa) 2% - 2 ml,
3 ampoules;
- magnesium sulfate 25% - 10 ml, 5 ampoules;
- metamizole sodium (baralgin) - 2 ml, 2 ampoules;
- papaverine hydrochloride (or platifillin) 2% - 2 ml, 5 ampoules.

According to the NNPOSMP data, in Russia, in the practice of emergency care, the most common causes of acutely developed pain syndrome are back pain, renal colic, oncogenic pain.

The Indian health care system is rich in curious paradoxes. The development of cardiovascular surgery or other high-tech industries, at least in some cities in India, is on par with any developed country in the world. But literally across the street from those hospitals, you can easily see hundreds of people who are denied even first aid. And pain relief is no exception in this situation. About a million cancer patients in India who suffer from pain do not receive appropriate treatment. The number of people suffering from other types of chronic pain generally remains unknown. And not only in India. The situation is generally typical for most developing countries.

Any development of medical practice requires that the initiative come from the specialist or from the hospital administration. Pain relief is not as attractive to them as, for example, cardiovascular surgery. The hospital administration does not consider this an important task. Infectious disease control, for example, is a priority in the health care system, but pain management is not.

But the overall situation should be different. The number of people suffering from pain in society is always high. And even excessively. Most cases of chronic pain can be effectively controlled with simple and inexpensive methods. And it is very important for us, as specialists, to convey this to the administrator and develop in him a certain interest in this problem.

First of all, the main task of the pain treatment center is to demonstrate the effectiveness of treatment. Unfortunately, sometimes even interested specialists or entire institutions often do not realize the main meanings of this direction. Most specialists try to treat pain alone, using the methods with which they are most familiar and most skilled. The anesthesiologist uses regional blocks, the acupuncturist tries to treat any pain with acupuncture, and the physiotherapist trusts only his techniques. This approach is often doomed to failure.

Pain management requires a multidisciplinary approach. Ideally, in addition to the doctor and nurse, a psychologist should also be involved in the treatment of pain, and the choice of the method of therapy should be discussed with the patient or relatives. However, such an ideal model cannot be achieved in practice. Several specialists per patient appointment is a utopian dream that can never be realized, given their busy schedule.

The solution lies in the doctor's understanding of the importance of a multidisciplinary approach to pain management. Doctor general practice should be prepared to treat pain as a specialist. Looking at the problem from the point of view of the patient, he must be able to assess the pain and the degree of the emotional component in the formation of pain, choose the necessary method of pain treatment, and, if necessary, refer the patient for a consultation with a specialist.

Pain treatment

Since the assessment of the intensity of the pain syndrome is always more clinical, there is no significant difference in how it is carried out in developing and developed countries. It is necessary to distinguish between nociceptive and neuropathic pain. It is also important to remember that pain is not just a sensation. Pain is "a combination of sensitive and emotional components". Physical pain will inevitably change under the influence of social, emotional and mental factors. Therefore, attempts to treat chronic pain only as a physical component will always be ineffective. Every pain specialist needs to keep this in mind. It is always important to establish a trusting relationship with the patient. "The pain that the patient talks about is always only to his evil."

The World Health Organization (WHO) three-step ladder (Figure "World Health Organization (WHO) Pain Management Ladder") has revolutionized cancer pain management worldwide.

It involves the use of analgesics orally by the hour, depending on the duration of the drug. Stage I uses non-opioid analgesics such as paracetamol or NSAIDs. If the effect is insufficient, weak opioids, such as codeine or dextropropoxyphene, are added. If this fails to control the pain, the weak opioid is changed to a strong one, like morphine.

The most important principles when using the World Health Organization (WHO) ladder in practice are:

♦ Give all drugs by mouth whenever possible. Doing injections for a long time is very inconvenient and usually causes discomfort to the patient.

♦ When taken orally, the risk of developing allergic reactions including bronchospasm.

♦ Since all of these drugs are effective only when taken regularly, follow the recommendations for frequent use.

♦ Prescribe analgesics strictly by the hour, depending on the time of action of each drug.

I stage of pain treatment

For mild pain of an obviously nociceptive nature, a simple analgesic, such as paracetamol, is excellent if given regularly, say every 4-6 hours. No other analgesic has such a low potential hazard that it can be used long time in very high (up to 4-6 g / day) doses. Proper use of paracetamol significantly reduces the dose of stronger drugs.

Frequency of prescription of NSAIDs in the treatment of pain

A drug	Appointment time
Aspirin	Every 4-6 hours
ibuprofen	6-8 hours
Diclofenac	8-12 hours
Ketorolac	6-8 hours
Meloxicam	24 hours
Rofecoxib	24 hours

Most oral NSAIDs in the treatment of chronic pain can be successfully used for a long time.

However, the most important side effects must also be kept in mind:

♦ gastritis (if it occurs, H 2 blockers are prescribed in parallel)

♦ platelet dysfunction

♦ development of nephropathy in patients with a predisposition

II stage of pain treatment

If paracetamol or NSAIDs alone are not enough to control pain, a weak opioid should be included in stage II.

The most available analgesics of this group in India, recommended doses and required frequency of prescription:

Recommended doses and frequency of weak opioids for pain management

A drug	Appointment time
Codeine 30-60 mg	Every 4 hours
Dextropropoxyphene 65 mg (usually only given in combination with paracetamol)	6-8 hours
Tramadol 50-100 mg	6-8 hours
Buprenorphine (0.2-0.4 mg sublingually) (Buprenorphine is a strong opioid in some countries)	6-8 hours

Dextropropoxyphene is the most widely available of all. Tramadol is a stronger drug, but expensive. Pentazocine is also available for oral use but is not recommended because it can cause dysphoria and has a too short duration of action. Due to significant problems with the availability of oral forms of morphine in our country, weak opioids occupy a special position in the treatment of cancer pain. But, unfortunately, they all have a "ceiling effect". This means that their dose can only be increased up to a certain point and limits their use in severe pain.

Stage III pain management

With the ineffectiveness of stage II therapy, weak opioids are changed to strong ones.

Oral morphine is the mainstay of treatment for severe chronic pain. Contrary to popular belief, oral morphine, when used for the treatment of opioid-sensitive pain with careful dose adjustment, does not cause addiction or respiratory depression. An alarm signal when prescribing a high dose will be the appearance of excessive drowsiness, delirium or convulsions.

The usual starting dose is 5-10 mg. If necessary, the dose is increased by 50% every 12 days until the desired effect is obtained.

The most common side effects of opioids include:

♦ Constipation.

Almost all patients receiving opioids require laxatives. The drugs of choice in this situation would be stimulant laxatives such as bisacodyl or senna. It may be useful to add liquid paraffin or other emollient to therapy.

♦ Up to one third of patients will complain of nausea and require antiemetics.

♦ During the first few days of therapy, about a third of patients feel fatigue. Some pay attention to a sharp decrease in appetite, up to anorexia.

♦ Urinary retention is a relatively rare side effect.

♦ Skin itching.

Usually resolves within a few days after starting antihistamine therapy.

When you can not use I and II steps

The number of pain clinics in India can be counted on the fingers, so we often see patients suffering from sometimes excruciating pain for a long time. In such situations, the concept of the World Health Organization (WHO) ladder for pain management obviously needs to be modified. On the one hand, intravenous boluses of morphine every ten minutes at 1.5 mg can be tried until the pain decreases or the patient becomes drowsy. The occurrence of drowsiness while maintaining the pain syndrome indicates the presence of pain that is poorly sensitive to opioids. An alternative to intravenous morphine for excruciating pain is to give it orally at 10 mg every hour until the desired effect. It should be emphasized that in the treatment of severe tumor pain, it is sometimes necessary to bypass the first two steps of the ladder.

Availability of oral morphine for pain management

In India, a paradoxical situation is emerging. We supply opium to other parts of the world for medical purposes while our own patients suffer for want of morphine. Responsible in this situation are the state bodies exercising strict, sometimes too strict control over the circulation of narcotic drugs in the country. Currently, the provisions in the system of control over the circulation of narcotic drugs are being simplified. Seven states in India today simplified control, which made oral forms morphine is much more accessible. In other states, complex licensing systems are still a necessity.

Adjuvants in the treatment of opioid-resistant pain

Adjuvants are drugs that do not have a specific analgesic effect, but their administration contributes to significant pain relief. Opioids are not always able to adequately relieve pain. Prescribing morphine to such a patient only exacerbates his suffering by causing dizziness, fatigue, delirium, or muscle rigidity.

Examples of relatively opioid-resistant pain include:

♦ muscle pain(in some cases it is necessary to use muscle relaxants and injections into myofascial trigger points)

♦ Spasmodic pain (good effect achieved by the appointment of antispasmodic drugs, such as dicyclomine or hyoscine butylbromide)

♦ joint pain(in this situation, opioid administration should be combined with NSAIDs, and in some cases with corticosteroids)

♦ Pain with constipation

♦ neuropathic pain

Basic principles for the treatment of neuropathic pain

The main groups of drugs used in its treatment are anticonvulsants and antidepressants. Both of them can become first-line drugs. Antidepressants are better tolerated and in many clinics it is with them that they begin therapy. With the simultaneous appointment of representatives of these two groups enhance the action of each other.

Commonly used doses of these drugs:

Commonly used doses of anticonvulsants and antidepressants in the treatment of neuropathic pain

Anticonvulsants
Carbamazepine	200-400 mg every 8 hours
Phenytoin	200-400 mg per day
sodium valproate	up to 1200 mg
Tricyclic antidepressants
Amitriptyline	25-75 mg at bedtime
Doxepin	25-75 mg at bedtime

Since they all cause significant side effects, the starting dose should be small and increased gradually. Start treatment of side effects promptly.

The action of anticonvulsants is based on membrane stabilization. It is possible that sodium valproate also affects GABA metabolism. Tricyclic antidepressants block the reuptake of serotonin and norepinephrine, increasing their concentration in synapses.

When first-line therapy fails, other methods are used. One of them is the oral administration of mexiletin, a drug from the group of local anesthetics. As a test, intravenous administration of lidocaine at a dose of 1 mg/kg is used. If an analgesic effect occurs and persists for more than 20 minutes (short local anesthesia may be due to the placebo effect), oral mexiletine can be started on a regular basis.

Ketamine hydrochloride, a blocking anesthetic, has also been used successfully in the treatment of neuropathic pain refractory to conventional therapy. It is prescribed orally at 0.5 mg / kg every 6 hours with a gradual increase in dose. When using ketamine, the physician may encounter significant side effects such as delusions and hallucinations. Amantidine, an antiparkinsonian agent, is also an NMDA antagonist and may be effective in the treatment of neuropathic pain. Used at a dose of 50-100 mg daily.

Corticosteroids are used for radicular and compression syndromes, as well as for pain associated with an increase in intracranial pressure. They can be administered systemically, but with regional administration (for example, epidural), the effect is much better. With systemic administration, dexamethasone is preferred, triamcinolone is the drug of choice for epidural blockade.

Some local procedures may also be used in the treatment of neuropathic pain. With severe skin hyperalgesia, it can be very effective topical application capsaicin. If the nerve is preserved proximal to the site of damage, the use of transcutaneous electrical nerve stimulation (TENS) will be useful. With complex regional pain syndrome (CRPS) of the upper limb, regular blockade of the stellate ganglion with local anesthetics is recommended.

In the absence of the effect of conservative medical therapy, prolonged epidural analgesia or neurolytic procedures can be used. For example, blockade of the celiac plexus in tumors of the upper abdominal cavity. It is also appropriate in the case when the patient came for examination and selection of therapy from afar. If standard techniques do not respond well, consider using alternative adjuvants, such as thoracic epidural alcohol for thoracic or upper abdominal malignancy.

Basic principles of pain management

The following points may be helpful for a doctor who decides to devote himself to helping people suffering from pain:

♦ Determining the type of pain is the main key to successful pain management.

The main directions in the treatment of neuropathic pain, for example, differ from the therapeutic measures used to treat articular pain syndrome.

♦ Remember that any pain that persists for a long time can be fixed at the central level.

The ability of nervous tissue to undergo anatomical and even genetic changes is described. As soon as the central level of pain control is formed, peripheral methods of treatment (for example, conduction blockade) will no longer be effective.

♦ Somatization.

When negative emotions, for example, in the form of fear or anger, come to the fore along with the physical manifestations of pain, one speaks of its "somatization". Quite often this irritates the doctor. Remember that the patient is not to blame. Behind the pain, certain emotional experiences can also be hidden. The doctor will have to figure it out and prescribe the appropriate treatment.

♦ If a certain procedure, such as a regional blockade, would be appropriate in a particular case, then drug therapy is usually the ideal basis for pain management in most patients.

♦ It is obvious that the optimal type of therapy (from the doctor's point of view) under certain conditions may not be suitable for a particular patient.

When planning treatment, it is always necessary to take into account the financial capabilities of the patient.

Organization of a pain treatment service

Any attempt to address pain in a developing country must take into account the need for therapy and economic realities. We see that about 80% of patients who visit pain clinics suffer from cancer-related pain. To help such patients, in most developed countries there are two parallel services. First of all, these are pain clinics, where anesthesiologists work, as well as a "hospice system" or palliative care for cancer patients. Unfortunately, in India, as in most developing countries of the world, despite the high demand, none of these services is developed. It is possible that their integration will be the most practical solution for us.

When opening a palliative care service in Calicut, we relied on the following principles:

♦ Put the patient's need first.

The needs of the patients must be a priority. This may sound obvious, but is not always the case in practice. We ourselves must understand that if the patient does not need to improve the quality of life, there will be no one to provide assistance.

♦ The system of assistance must be real.

It should fit the local cultural and economic background.

♦ When starting treatment, the doctor needs to establish contact with the patient's family.

A strong family structure is what our country is proud of. Much can be achieved by empowering relatives to monitor the patient.

♦ A confidential conversation should be held with the patient.

An ordinary villager is quite capable of making a decision and choosing a treatment method. Education and intelligence are not synonymous. The doctor has no right to make decisions for the patient.

♦ Use all available resources.

Healthcare in India is represented by a network of first, second and third order centers. All of them have their advantages and disadvantages. Always use only necessary products for treatment. A competent choice of the necessary type of therapy is also justified economically.

♦ Pain treatment gaps should be filled from non-government sources.

To do this, you need to have access to them. The joint work of the public health system and non-governmental funds or organizations for the treatment of pain is very useful, first of all, for the patient.

♦ Volunteers can be a key element in helping people with pain.

These are selfless people, with a good heart, having a desire to help others. The only thing that is needed is to properly organize and direct their actions in the right direction.

Pain Management Experience in Calicut

In Calicut, a small town in the state of Kerala in southern India, we organized a pain treatment service, which can be represented as a kind of pyramid, where the patient is at the top, relatives and volunteers are below. At the base, supporting them, lies the medical system, represented by state and non-state organizations. The clinic is affiliated with the State Medical College Hospital and is supported by the Society for Pain and Palliative Care, a charity based in Calicut.

Its tasks include recruiting volunteers, training staff, providing equipment and analgesics in situations where public services are powerless.

Over the past eight years, our service has grown significantly and has reached an average of 2,000 patients per year at the main clinic located in Calicut. Daily needed help receive about 60 people, and every month about 100-130 new patients are registered for an appointment. We are working with doctors from remote areas and non-governmental foundations to establish local branches of the clinic. There are already 27 such clinics operating effectively in various districts of our state. Some of them even have home visiting programs designed to help critically ill non-transportable patients. We estimate that 15% of the total number of people in need of palliative pain treatment in Kerala are currently receiving it.

Much has been achieved in these eight years, but there are still about a million people in India in need of pain relief. You don't need expensive drugs or complex sophisticated methods to help them. Morphine, made from poppies grown in India, a few other not too expensive drugs, and most importantly, the understanding of health officials that a person has the right to get rid of pain is all that is needed for this.

additional literature

1. IASP Subcommittee on Taxonomy. Pain terms: a list with definitions and notes on usage. Pain 1980;8:249-52.

2. Black R.G. The Chronic Pain Syndrome. Surgical Clinics of North America 1975;55:999-1011

3. World Health Organization. Cancer Pain Relief. WHO. 1986

4. Twycross R. Introducing Palliative Care. Radcliffe Medical Press. Oxford. 1999

5. Sureshkumar K, Rajagopal MR, Naseema AM. Intravenous morphine for emergency treatment of cancer pain. Palliative Medicine 2000;14:183-188

6. Expert Working Group of the European Association for Palliative Care. Morphine in cancer pain: modes of administration. British Medical Journal 1996;312:823-826

7 Rajagopal MR, Joranson DE, Gilson AM. Medical use, misuse and diversion of opioids in India. The Lancet 2001;358:139-143

8. Woodruff R. Palliative Medicine: Symptomatic and Supportive Care for Patients with Advanced Cancer and AIDS. Oxford University Press, Melbourne. 1999

9. Kalso E, Tramer HJ, McQuay, et al. Systemic local-anaesthetic-type drugs in chronic pain: a systematic review. European Journal of Pain 1998;2:3-14

10. Fisher K, Coderre TJ, Hagen NA et al. Targeting the N-Methyl-D-Aspartate Receptor for Chronic Pain Management: Preclinical Animal Studies, Recent Clinical Experience and Future Research Directions. Journal of Pain Symptom Management 2000;5:358-73

11. Pud D, Eisenberg E, Spitzer A et al. The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double blind, randomized, placebo controlled trial. Pain 1998;75:349-354

12. Korevaar WC. Transcatheter epidural neurolysis using ethyl alcohol. Anesthesiology 1988;69:989-93.

13. Sureshkumar R, Rajagopal MR. Palliative Care in Kerala. Problems at Presentation in 440 patients with advanced cancer in a South Indian state. Palliative Medicine 1996; 10:293-8

14. Rajagopal MR, Sureshkumar. A model for delivery of palliative care in India - The Calicut Experiment. Journal of Palliative Care 1999;15:44-49

15. Ajithakumari K, Sureshkumar K, Rajagopal M R. Palliative Home Care - The Calicut Experiment. Palliative Medicine 1997;11:451-454

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Pain is an important protective biological phenomenon, which mobilizes all the functional systems necessary for the survival of the organism, allowing to overcome the harmful effects that provoked it, or to avoid them.
About 90% of all diseases are associated with pain. She is the root medical terms: illness, hospital, patient.
In various regions of the world, from 7 to 64% of the population experience pain periodically, and from 7 to 45% suffer from recurrent or chronic pain.

However, under normal conditions, a person does not feel pain due to the harmonious balance between the nociceptive (conducting pain afferentation) and antinociceptive (suppressing pain afferentation that does not go beyond physiologically acceptable limits in intensity) systems.
This balance can be disturbed by a short but intense nociceptive afferentation or a moderate but prolonged nociceptive afferentation. The possibility of insufficiency of the antinociceptive system is discussed less often, when physiologically normal nociceptive afferentation begins to be perceived as pain.

The temporal aspect of the imbalance between the nociceptive and antinociceptive systems distinguishes between:

transient pain
sharp pain
chronic pain

Transient pain provoked by activation of nociceptive receptors in the skin or other tissues of the body in the absence of significant tissue damage and disappears before it is completely healed. The function of such pain is determined by the rate of occurrence after stimulation and the rate of elimination, which indicates that there is no danger of a damaging effect on the body.
In clinical practice, for example, transient pain is observed during intramuscular or intravenous injection.
It is assumed that transient pain exists to protect a person from the threat of physical damage by environmental factors in the form of a kind of training of the antinociceptive system for an adequate response, i.e., the acquisition of pain experience.

acute pain

acute pain- a necessary biological adaptive signal about a possible (in the case of pain experience), incipient or already occurred damage. The development of acute pain is associated, as a rule, with well-defined pain irritations of superficial or deep tissues and internal organs or a violation of the function of smooth muscles of internal organs without tissue damage.
The duration of acute pain is limited by the recovery time of damaged tissues or the duration of smooth muscle dysfunction.
Neurological reasons acute pain can be:

traumatic
infectious
dysmetabolic
inflammatory
and other damage to the peripheral and central nervous system, meninges, short neural or muscle syndromes.

Acute pain is divided into:

superficial
deep
visceral
reflected

These types of acute pain vary in subjective sensations, localization, pathogenesis and for reasons.

Superficial pain, arising from damage to the skin, superficial subcutaneous tissues, mucous membranes, is felt as a local acute, stabbing, burning, throbbing, piercing. It is often accompanied by hyperalgesia and allodynia (feeling of pain with non-painful stimuli). Deep pain occurs when the nociceptors of muscles, tendons, ligaments, joints and bones are irritated. It has a dull, aching character, is localized less clearly than superficial.
One or another localization of pain in case of damage to deep tissues is determined by the corresponding spinal segment that innervates the tendons, muscles, ligaments. Structures innervated from the same segment can cause the same localization of pain.
Conversely, closely spaced structures, innervated by nerves originating from different segments, also cause pain that differs in localization.
In accordance with the segmental innervation of damaged tissues, skin hyperalgesia, reflex muscle spasm, autonomic changes accompanying deep pain are also localized.

Visceral pain are caused by involvement in the pathological process of either the internal organs themselves or the parietal peritoneum and pleura covering them. Pain caused by diseases of the internal organs (true visceral pain) is unclear, dull, aching in nature.
They are diffuse, poorly defined topographically. Often accompanied by parasympathetic manifestations: nausea, vomiting, sweating, low blood pressure, bradycardia.

Another variant of pain that occurs in the pathology of internal organs is referred pain. Reflected pains, or the Ged-Zakharyin phenomenon, are projected into dermatomes innervated by the same segments as the deeply located tissues or internal organs involved in the pathological process.
At the same time, local hyperalgesia, hyperesthesia, muscle tension, local and diffuse vegetative phenomena occur, the severity of which depends on the intensity and duration of the pain effect.

Intense and prolonged muscle tension (“spasm”) can become an independent cause that intensifies pain, which must be taken into account in the treatment of referred pain.

chronic pain

chronic pain in neurological practice, the condition is much more relevant. There is no consensus on what is meant by chronic pain. According to some authors, this is pain lasting more than three months, according to others - more than 6 months. In our opinion, the most promising is the definition of chronic pain as pain that continues after a period of healing of damaged tissues. In practice, this may take several weeks to six months or more.

Chronic pain can also include recurring pain conditions (neuralgia, headaches of various origins, etc.). The point, however, is not so much in temporal differences, but in qualitatively different neurophysiological, psychological and clinical features.
The main thing is that acute pain is always a symptom, and chronic pain can become essentially an independent disease. It is clear that the therapeutic tactics in the elimination of acute and chronic pain has significant features.
Chronic pain in its pathophysiological basis can have a pathological process in the somatic sphere and / or primary or secondary dysfunction of the peripheral or central nervous system, it can also be caused by psychological factors.

Untimely and inadequate treatment of acute pain can become the basis for its transformation into chronic pain.

Nociceptive afferentation exceeding the physiological threshold is always accompanied by the release of algogenic compounds (hydrogen and potassium ions, serotonin, histamine, prostaglandins, bradykinin, substance P) into the intercellular fluid surrounding the nociceptors.
These substances play a key role in the formation of pain caused by damage, ischemia and inflammation. In addition to the direct excitatory effect on the membranes of nociceptors, there is an indirect mechanism associated with impaired local microcirculation.

Increased capillary permeability and venous stasis contribute to the extravasation of active substances such as plasma kinins and serotonin.
This, in turn, disrupts the physiological and chemical environment around the nociceptors and increases their excitation.
The continued release of inflammatory mediators can cause prolonged impulses with the development of sensitization of nociceptive neurons and the formation of "secondary hyperalgesia" of the damaged tissue, contributing to the chronicity of the pathological process.

Any peripheral pain is associated with an increase in the sensitivity of nociceptors due to the release of inflammatory substances. An increase in the sensitivity of the primary nociceptor in the affected peripheral tissue leads to an increase in the activity of neurons that send impulses to the spinal cord and the central nervous system, however, spontaneous electrical activity can be generated in the focus of neurogenic inflammation, causing a persistent pain syndrome.

Such a powerful inducer of pain sensitivity are pro-inflammatory components: bradykines, histamine, neurokinins, nitric oxide, which are usually found in the focus of inflammation. Prostaglandins themselves are not pain moderators, they only increase the sensitivity of nociceptors to various stimuli, and their accumulation correlates with the development of inflammation intensity and hyperalgesia.
Prostaglandins, as it were, mediate the involvement of "sleeping" nociceptors in the formation of secondary inflammatory hyperalgesia and peripheral sensitization.

Concepts of secondary hyperalgesia, peripheral and central sensitization essentially reflect the pathophysiological mechanisms of chronic pain syndrome, behind which there is a whole cascade of neurophysiological and neurochemical transformations that ensure the maintenance of this state.

Hyperalgesia, which is an enhanced response to a normal noxious stimulus and is often associated with allodynia, has two components: primary and secondary.

Primary hyperalgesia is associated with the site of tissue damage and occurs mainly in connection with processes occurring locally. Nociceptors become oversensitive due to substances released, accumulated or synthesized at the site of injury (peripheral sensitization). These substances include serotonin and histamine, neurosensory peptides (SR, CGRP), kinins and bradykinins, arachidonic acid metabolism products (prostaglandins and leukotrienes), cytokines, etc.

Secondary hyperalgesia is formed due to the involvement of "sleeping" nociceptors in the pathological process..
With an adequate relationship between the nociceptive and antinociceptive systems, these polymodal receptors are inactive, but become active following tissue damage (under the influence of histamine, serotonin and bradykinin released as a result of degranulation mast cells following the release of neurosensory peptides).
In the central nervous system, increased afferent impulses from sensitized and newly activated dormant nociceptors lead to increased release of activating amino acids (glutamate and aspartate) and neuropeptides in the dorsal horns of the spinal cord, which increases the excitability of central neurons.
As a result, the peripheral zone of hyperalgesia expands. In this regard, the initially subthreshold afferentation from the tissues adjacent to the injury now becomes suprathreshold due to an increase in excitability (i.e., a decrease in the threshold) of the central neurons.
This change in central excitability refers to the concept of "central sensitization" and causes the development of secondary hyperalgesia. Peripheral and central sensitization in chronic pain conditions coexist, are somewhat independent and, from the point of view of therapeutic measures, can be blocked separately from one another.

Mechanisms of Chronic Pain, depending on the predominant role in its genesis of different parts of the nervous system, are divided into:

peripheral
central
combined peripheral-central
psychological

Peripheral mechanisms mean constant irritation of the nociceptors of internal organs, blood vessels, the musculoskeletal system, the nerves themselves (nociceptors nervi nervorum), etc.
In these cases, removing the cause - effective therapy ischemic and inflammatory process, arthropathic syndrome, etc., as well as local anesthesia, leads to pain relief.
The peripheral-central mechanism, along with the participation of the peripheral component, suggests an associated (and / or caused by it) dysfunction of the central nociceptive and antinociceptive systems of the spinal and cerebral level. At the same time, long-lasting pain of peripheral origin can be the cause of dysfunction of the central mechanisms, which necessitates the maximum effective elimination peripheral pain.

Principles of pain management

Pain management includes identification and elimination of the source or cause that caused pain, determining the degree of involvement of various parts of the nervous system in the formation of pain and the removal or suppression of acute pain.
Therefore, based on the general principles of pain therapy, first of all, the effect is on its source, receptors and peripheral fibers, and then on the posterior horns of the spinal cord, the pain conducting systems, the motivational-affective sphere and the regulation of behavior, i.e. on everything levels of organization of the pain system.

Treatment of acute pain involves the use of several main classes of drugs:

simple and combined analgesics
nonsteroidal or steroidal anti-inflammatory drugs

An alternative to outdated analgesics, for example, can be considered a new generation of combined analgesics, such as Caffetin ® - one of the drugs that best meet these requirements and is designed to relieve acute pain of moderate and moderate intensity.
The composition of the drug includes caffeine, codeine, paracetamol and propyphenazone, which have analgesic, antipyretic and mild anti-inflammatory effects.
The mechanism of their action is associated with the ability to inhibit the synthesis of prostaglandins with an effect on the thermoregulatory center in the hypothalamus.
Caffeine stimulates the processes of excitation in the cerebral cortex (like codeine) and increases the analgesic effect of other components of the drug. The effectiveness of such drugs is confirmed by practice: it is possible to overcome pain, it is enough just to choose the right drug.

In addition, it should be noted that Caffetin® is approved for use as an over-the-counter drug, but the simultaneous use of analgesics with sleeping pills and alcohol.

The treatment of chronic pain syndromes is a more complex task that requires an integrated approach. The first line drugs in this case are tricyclic antidepressants, among which both non-selective and selective serotonin and norepinephrine reuptake inhibitors are used. The next line of drugs are anticonvulsants.
The experience available today has proven the need to treat patients with chronic pain in specialized centers of inpatient or outpatient type with the involvement of neurologists, therapists, anesthesiologists, psychologists, clinical electrophysiologists, physiotherapists, etc.

The main principle of the treatment of acute pain provides for a clinical assessment of the state of the neurophysiological and psychological components of the nociceptive and antinociceptive systems and the impact on all levels of organization of this system in order to prevent chronic pain syndrome when the dominant clinical component become psychological aspects experiences of social maladjustment, leading to a deterioration in the quality of life.

Neuropathic pain - diagnosis, rule - "Three" C "

Pain is evaluated in terms of etiology (trauma, burn, disease), duration (acute, chronic), localization (local, diffuse), intensity (severe, moderate, weak) ...

Pain - types of pain, choice of drugs for pain treatment

One of the most common symptoms in patients of any profile is pain, since it is often its presence that forces a person to seek medical help ....

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