Principles of treatment of chronic pain. Chronic pain

UDC: 619:616-089.5-036

The article describes the types of pain assessment and recognition and methods of its treatment. In the article methods of pain estimation and recognition and ways of its treatment are described.

According to the International Association for the Study of Pain (IASP), pain is an unpleasant sensory or emotional experience associated with actual or potential tissue injury.

To properly understand the principles of pain treatment, it is necessary not only to know the characteristics of physiological processes, the anatomy of the nervous system, pharmacology, and the principles of pain assessment. The recognition of the presence of pain as a problem in a veterinarian’s patient and an understanding of the relevance of adequate pain relief as a necessary component of the successful treatment of a huge number of diseases should come to the fore.

In medical practice, there is a special algorithm RAT - Recognize Assessment Treatment - recognition, assessment and treatment of pain. As with any algorithm, following the steps is of fundamental importance. If we skip the first step (recognition), we will not be able to begin treatment for the pain syndrome, since we will not know about its presence. If we do not evaluate pain (its type, intensity), then we will not be able to prescribe the correct treatment methods and assess the dynamics of pain correction. In veterinary practice, we are guided, first of all, by the recommendations of the WSAVA Pain Management guidelines.

In this article we will look at the methods by which we can recognize pain, the principles of assessing the type of pain syndrome, and treatment tactics for different types of pain syndromes.

Pain Recognition

This stage is one of the most difficult in the work of a veterinarian. Firstly, not all doctors recognize the very possibility of pain syndromes in animals. Secondly, to recognize pain, it is necessary to carry out a number of tests during the examination of the patient, which may not always provide obvious information. Our patients cannot say exactly where they have pain. Patients are often small and pinpointing the location of pain by palpation can be very difficult. Sometimes pain is excessively manifested in patients with an unstable emotional background.

To successfully recognize the presence of pain, we can use well-researched techniques.

The WSAVA Pain Management guidelines provide tables of pathologies with expected pain severity. These are very convenient tables so that you can quickly navigate the likelihood of pain in a patient with a specific pathology or, for example, after a planned operation. Such an understanding will allow one to quickly determine whether the patient will require active analgesia in the postoperative period, how long hospitalization for pain may be required, and whether multimodal analgesia is needed. The presented pathologies are divided according to the severity of the pain syndrome, starting with moderate pain and ending with severe, debilitating pain.

Moderate severe pain
immune-mediated arthritis	panostitis
capsular pain due to organomegaly	genital stretching
traumatic diaphragmatic hernia
trauma (orthopedics, head, extensive soft tissue injuries)	frostbite
obstruction of the ureter, common bile duct	corneal sequestration/ulcer
glaucoma, uveitis	IVD diseases
volvulus of mesentery, stomach, spermatic cord	septic peritonitis
	oral cancer
extensive resection or reconstructive surgery (osteotomy, open arthrotomy, ACL surgery)	dystocia

Also, to identify pain syndrome, you can use special test systems - pain rating scales. Work with such scales in medicine is very well organized, because an objective assessment of the severity of pain directly from the patient is possible. In veterinary practice, we are faced with the problem of the impossibility of objective assessment of pain. Therefore, they should use the most expanded scales, thereby increasing their sensitivity.

The most convenient for practical use is the Visual Analog Pain Scale, developed for dogs and cats. Using this scale, you can evaluate the severity of the pain syndrome on a scale from 0 to 4 using: 1) visual coincidence; 2) descriptions of behavioral changes; 3) descriptions of examination data (mainly using palpation).

The idea of working with such a scale is as follows: during the initial assessment of pain, a pain score is recorded (for example, 4). Based on this, the patient is prescribed analgesic therapy. Next, pain is reassessed on a scale, depending on the severity of the pain syndrome, after 1–4 hours. If the new assessment remains the same, it is reasonable to expand analgesic therapy, increase drug dosages, and consider non-drug methods of pain relief. If, with a new assessment, the score decreases to satisfactory (0–1), then analgesia can be considered successful and it can be continued at the same pace for some more time, based on the logic of the disease in this patient. Also, an important point in working with a pain rating scale is the mandatory assessment by one operator for as long as possible, this reduces the risk of increasing the subjectivity of the assessment.

All of these tables and scales are suitable for assessing acute pain in a clinical setting and should be administered by trained personnel (physician, technician or assistant).

The assessment of chronic pain syndrome is a much more complex process. A huge number of manifestations of chronic pain in people are described precisely by sensations - for example, twitching in the fingers, or coldness of the tip of the nose, pressing circular pain in the head. It is clear that we cannot evaluate such manifestations in animals. To assess the course of chronic pain in animals it is necessary: 1) to determine the very probability of the presence of chronic pain. To do this, you need to remember about pathologies and diseases that are accompanied by chronic pain or can lead to its appearance; 2) use close contact with the owner to assess pain. For some diseases, there are developed scales for assessing chronic pain. For example, the largest body of research to date is on canine osteoarthritis. To monitor pain in these patients, diaries are used to complete at home by the owner or staff who regularly care for the individual patient. When visiting a doctor, the owner presents such a short diary, on the basis of which one can draw a conclusion about the effectiveness of the chosen therapy.

There are developed scales for assessing the quality of life of a cancer patient, but they are not yet freely available for use.

To monitor a patient receiving pain therapy at home, recommendations for behavioral changes can be made to owners according to the WSAVA Pain Management guidelines. For cats, it is important to assess general mobility (ease of movement, smoothness), the presence of activity and activity (playing, hunting, jumping, using equipment), the ability to eat and drink, the presence of self-care (scratching post, licking), the ability to relax, rest, exercise social events involving people and other pets, changes in temperament (usually for the worse). For dogs, slightly different recommendations. It is important to assess activity and mobility (energy in movement, happiness when moving, playfulness, ease of changing posture, tolerance of movements and exercises), mood and behavior (alertness, anxiety, sadness, playfulness), determine the level of stress control (vocalization, depression, reaction on other dogs and people). The dog may also have visible signs of pain - lameness, decreased comfort level, for example, when changing position.

Diseases accompanied by chronic pain in dogs and cats

Assessment of pain type: acute and chronic

Acute pain is a pain syndrome that develops in response to acute tissue damage and has, first of all, a protective and adaptive evolutionary function. For example, if a person grabs a hot frying pan, then due to the formation of an acute pain syndrome, he will: 1) throw the frying pan away and thus carry out a protective function; 2) will transmit information to their descendants and society to carry out the adaptive function. On the other hand, if this burn is not treated correctly, deep necrosis of the skin and underlying tissues will develop, trauma to the nerve endings in this area will develop, impulses along the nerve fibers will not pass correctly, a change in the function and structure of the nervous tissue at the local level will develop - this person will develop chronic pain.

Thus, we define acute pain syndrome as a rapidly developing process with acute symptoms in response to direct damage (mechanical, thermal, chemical). And chronic pain syndrome is a long-term process associated with secondary damage to tissue and nerve endings. Another important difference is the location of the pain. In acute pain, we can precisely localize the source of pain (for example, a broken limb). With chronic pain, precise localization is impossible (for example, with intervertebral disc disease, we can only roughly determine the pain in the neck or lower back, but not in a specific vertebra). In acute pain syndrome, the pain stops along with healing and elimination of the cause. While with chronic pain, the cause most often cannot be eliminated.

In many cases, we can avoid the formation of chronic pain syndrome provided that pain is successfully controlled during the acute period. According to some medical studies, a significant number of postoperative patients experience chronic pain:

– inguinal hernia 4–40%

– mastectomy 20–49%

– thoracotomy more than 67%;

– amputation more than 90%.

Severe acute pain is a predictor of chronic pain.

Of course, another situation is possible, when acute pain syndrome develops against the background of chronic pain. Such situations are the most difficult to treat, because symptomatically we see acute manifestations, and treatment will also require drugs that affect the course of chronic pain. The main example of this type of combined pain syndrome is severe abdominal pain during exacerbation of chronic pancreatitis.

Chronic pain, in turn, can be characterized as inflammatory (due to the long-term influence of inflammatory components from tissue injury or inflammation on nerve endings - for example, pain from pancreatitis) and neuropathic (pain that occurs directly from trauma to the nervous system - brain tumors brain, diseases of the intervertebral discs, cutting of large nerves during operations, etc.). Chronic pain can be suspected in patients who have long-term inflammatory diseases or diseases of the central nervous system. Or if the patient exhibits obsessive licking, scratching, and reacts inadequately to minimal painful manipulations or even to simple touches (manifestations of hyperalgesia and allodynia). Also, if the patient has a poor response to treatment with NSAIDs and opioids, the presence of chronic pain should be suspected. The approach to treating different types of chronic pain should also be different.

Physiology of pain

To better understand the processes of pain development and the principles of multimodal analgesia, it is necessary to know the basics of the formation of a pain signal in the body.

At the moment, the theory of the formation of the nociceptive arc, which is divided into several stages, is recognized in the world.

The first stage is transduction, that is, primary tissue damage and the formation of a pain impulse, which begins its movement along the sensory fibers to the posterior horns of the spinal cord - the transmission process. In the dorsal horn of the spinal cord, the pain impulse travels to the anterior horn through the synapses of nerve endings - this process is called modulation. The speed of passage of impulses and the neurotransmitters that are involved in their transmission from the posterior horns of the spinal cord to the anterior ones differ during the development of acute and chronic pain. These differences are very important in the selection of drug therapy. Next, the impulse from the anterior horns of the spinal cord passes to various structures of the brain, where this information is assessed - perception. If we are talking about the formation of acute pain, then an acute motor response will follow - withdrawing a limb, jumping away, biting, that is, a reaction aimed at protecting against the obvious cause of pain. If a process of chronic pain is formed, then a visible motor response will not occur. Firstly, due to the fact that the speed of impulse transmission during the formation of chronic pain is lower. Secondly, because when chronic pain develops, the source of pain itself is not clearly localized, therefore, the body has no way to protect itself from this source. Usually, when chronic pain syndrome develops, the symptoms are very minor; sometimes the doctor at the appointment may not even recognize these manifestations. Therefore, it is extremely important to qualitatively interview the owner of a patient in whom, due to the nature of the disease, you may suspect chronic pain syndrome, because data on minor changes in behavior and in the natural routine of the patient’s life may indicate the formation of chronic neuropathic or inflammatory pain.

At the stage of tissue damage (transduction), tissue inflammatory mediators - histamine, potassium, bradykinin, leukotrienes, prostaglandins, cytokines, serotonin - play an important role in the formation of pain. All these factors are called in one word - “inflammatory soup” and cause peripheral sensitization - that is, they affect peripheral nerve fibers, stimulating their endings and forming a pain impulse. Accordingly, to relieve pain, we must use medications and techniques that will reduce the severity of the manifestation of the primary injury, thus reducing the intensity of the effect on peripheral fibers and the likelihood of the formation of chronic changes in these fibers and chronic pain syndrome.

Directly at the synapses of the dorsal horns of the spinal cord, some receptors and excitation mediators - NMDA receptors, AMPA receptors, potassium channels, glutamate - are of greatest importance for the formation of acute pain syndrome. In the formation of pathological changes in the synapse, a large amount of glutamate (due to the continuous excitation of nerve fibers from the area of tissue damage), NMDA receptors, magnesium channels, protein C, nitric oxide, calcium in the intersynaptic cleft, substance P plays an important role. In the case of long-term influence on the synapse and the constant release of a large amount of glutamate into the synaptic cleft, the magnesium channel of the NMDA receptor is constantly open, and a large amount of calcium from the synaptic cleft penetrates through it. This calcium, influencing protein C, causes the formation of large amounts of nitric oxide, which, in turn: 1) closes potassium channels (through which opioid analgesics work, so they are ineffective in treating chronic pain; 2) release large amounts of substance P , which interacts with the gene structure of the synapse, causing its morphological irreversible changes. Thus, chronic pain syndrome is a manifestation of the morphological, pathologically altered structure of the nervous tissue and, in fact, a separate disease.

The principle of multimodal analgesia is to use techniques and drugs for pain relief that can interrupt the nociceptive arc at 2 or more stages, or that act at one stage, but on 2 or more different receptors.

Treatment of acute pain

Since we know that acute pain is always a quick response to direct damage, the main principle of treatment is the use of multimodality and elimination of damage. Various drugs and techniques can be used to relieve acute pain.

In the treatment of acute pain, it is important to adhere to the principle of maximum analgesia in order to prevent the patient’s suffering, improve his functionality, and prevent the development of chronic pain syndrome. Therefore, when relieving acute pain, it is important to anesthetize the patient as much as possible in the first 12–24 hours and only after that reduce the intensity of analgesia using scales for assessing the severity of pain.

Epidural analgesia

A method based on the introduction of local anesthetics (or a combination of anesthetics) into the epidural space to form a block above or at the level of tissue damage. This method can be used both to relieve pain during surgery (when pain is associated with acute surgical tissue damage) and in the treatment of patients with various pathologies as part of inpatient treatment. For example, with fractures of the limbs or pelvis, severe injuries of soft tissue from the perineal area or pelvic limbs, with acute pain from the pelvic or abdominal organs, with severe peritonitis of any etiology. Applications include intermittent administration by puncture into the epidural space or by insertion of an epidural catheter.

Additional pain-relieving techniques include the use of bracing (for example, bandaging for chest trauma, surgical bracing for dislocated joints or broken limbs), and the use of thermotherapy (for example, massage with cubes of frozen chlorhexidine 1% in areas with swelling or post-operative areas).

Drugs for the treatment of acute pain belong to different pharmacological groups: dissociative anesthetics (Tiletamine, Ketamine), alpha agonists (medetomidine, dexmedetomidine), non-steroidal anti-inflammatory drugs, muscle relaxants, central non-opioid analgesics, opioid drugs (available in veterinary practice with a license).

Tiletamine + zolazepam is a combination drug that consists of tiletamine (provides analgesia) and zolazepam (provides sedation). In terms of interrupting the arc of pain, the drug acts at the perceptual level in the brain. In dogs, the half-life of zolazepam is shorter than that of tiletamine, so when waking up, dogs sometimes experience tonic convulsions, vocalization, and restlessness. In cats, the half-life of zolazepam is longer than that of tiletamine, so cats often take a very long time to wake up. This drug can be used in intensive care practice for the relief of acute pain in mono mode with moderate to moderate pain (for example, with acute urinary retention, with pleurisy for thoracentesis, with short surgical treatment of wounds, etc.). Or as part of multimodal analgesia for severe, debilitating pain (after thoracotomy, in the treatment of severe pancreatitis or enteritis, after extensive removal of soft tissue, in severe trauma). This drug also provides great assistance in the initial diagnosis of a patient with trauma, when it is possible to achieve both pain reduction and moderate sedation sufficient for conducting quick diagnostic tests (ultrasound, X-ray, centesis). Dosages for bolus administration are 0.5–2 mg/kg intramuscularly or intravenously. For infusion at a constant rate, doses of 0.5–1 mg/kg/h can be used, but it is worth remembering the peculiarities of drug metabolism in different animal species.

Medetomidine and dexmedetomidine are very widely used for the treatment of pain in the acute period. These drugs are recommended for use in ISI (constant rate infusion) in patients with severe-debilitating pain as part of a multimodal analgesic regimen. In this case, the scope of their action from the point of view of interrupting the arc of pain is perception and modulation. They can also be used for introduction into the epidural space, in which case they will act at the transmission level. Both may have a sedative effect and may have an effect on blood pressure, so monitoring of the patient receiving such PPI treatment should be increased. Dexmedetomidine has a lesser effect on consciousness and hemodynamics, therefore it is safer and more promising for use in clinical practice. For IPS, the following doses can be used: medetomidine 0.5–2 mcg/kg/h, dexmedetomidine 0.25–1 mcg/kg/h.

Nonsteroidal anti-inflammatory drugs have an analgesic effect due to their influence on the formation of inflammation (by blocking cyclooxygenase and acting on other inflammatory mediators) in the area of damage and realize their effect at the transduction level. The scope of application is very wide, but in mono mode they can only be used for moderate to moderate pain (for example, cystitis or a simple fracture after osteosynthesis). They are also used as part of multimodal analgesia for more severe pain syndromes. Due to possible side effects (the development of erosions or ulcers in the intestines and stomach, the development of acute renal failure, the effect on the blood coagulation system), their use is possible only in hemodynamically stable patients with normal body temperature and only in recommended dosages and in compliance with the recommended frequency. In patients in shock, with recent polytrauma, and dehydration, the use of these drugs is limited. Below is a table with WSAVA recommended drugs, doses and frequency of use.

Karpofen	surgery		p/c, i/v, p/o, p/c, i/v, p/o	1/24 hour, up to 4 days 1/12 hour, up to 4 days
				once
	chronic			1/24 hour, titrated to minimum dose
Meloxicam	surgery			once
				once
	chronic

Ketoprofen		dogs and cats	i.v., s.c., i.m.	once after surgery 1/24 hour. up to 3 days

The muscle relaxant Tizanidine (sirdalud) is a centrally acting drug that acts in the dorsal horns of the spinal cord to inhibit the transmission of excitation, which influences the regulation of skeletal muscle tone, while muscle tone decreases. This effect gives good clinical results in patients with acute spinal pain and reflex muscle spasms. There are no known dosages for small pets, but empirical doses can be used, the effect of which can be assessed clinically: dogs 0.1–0.2 kg/kg, cats 0.05–0.1 mg/kg. If the dose is exceeded, lethargy, sedation, and decreased blood pressure can be observed.

Non-opioid analgesics of central action include flupirtine (catadolone), a potassium channel activator and an indirect NMDA receptor blocker. It has an analgesic effect, a muscle relaxant effect and prevents the processes of chronic pain syndrome due to the peculiarities of its influence in the synapses of neurons. It can be successfully used for the relief of acute pain in single mode with manifestations of moderate to moderate pain or as part of multimodal analgesia. There are no known dosages for dogs and cats; at the moment there are only studies of the pharmacokinetics of this drug in these groups of animals. You can use empirical doses of 3–5 mg/kg 2 times a day.

Opioid analgesics have limited availability in the Russian Federation due to the need to obtain a license. Opioid drugs interact with one of the types of opioid receptors and realize their effect through potassium channels in the synapse. They affect the conduction of pain in the peripheral fibers and in the central nervous system - in the dorsal horns of the spinal cord and in the brain. There are three types of opioid receptors - μ (mu receptors), δ (delta receptors) and κ (kappa receptors), and drugs can be their agonists, antagonists, agonist-antagonists, or partial agonists, respectively. The drugs can be administered intravenously, intramuscularly, or epidurally. The main side effects depend on the type of receptor. And often depending on the dose. These may include vomiting, dysphoria, nausea, bradycardia, sphincter urinary retention, respiratory depression, and shortness of breath. Dose-dependent effects are stopped by the opioid receptor antagonist, naloxone. They are used in mono mode for the treatment of moderate-moderate-severe pain or as part of multimodal analgesia.

Dogs, mg/kg

Cats, mg/kg

introduction

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 signaling damage to organs or tissues, but as a leading syndrome reflecting deep disturbances in the functioning of systems that carry out perception, conduct 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, and forms in the patient a special form of pain behavior, which persists even when the original triggering cause of pain is eliminated. Chronic pain, as defined by experts from the International Association for the Study of Pain, includes 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 damage to the structures of the nervous system;

Psychogenic, arising from mental disorders.

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

The development of nociceptive pain is based on the activation of nociceptors during injury, inflammation, ischemia or tissue edema. Clinical examples of such pain are post-traumatic and postoperative pain syndromes, arthritis, myofascial pain syndromes, pain due to tumor tissue damage, angina pain, pain due to 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 tissue, secondary hyperalgesia is localized outside the damaged area, spreading to healthy tissue. 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 dorsal horns of the spinal cord.

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

The development of neurogenic (neuropathic) pain syndromes occurs due to 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 in herniated intervertebral discs ). The most common causes of central neurogenic pain are considered to be traumatic injuries to the spinal cord and brain, ischemic and hemorrhagic strokes leading to a deficit of somatosensory sensitivity, demyelinating diseases (multiple sclerosis), syringomyelia, etc. In the clinical picture of neurogenic pain, regardless of the etiological factors and the level of damage As a rule, spontaneous pain is present, disturbances of tactile, temperature and pain sensitivity are detected in the form of hyperpathia, dysesthesia, allodynia, trophic changes in the skin, subcutaneous tissue, hair, nails, muscle tone or local autonomic disorders in the form of tissue swelling, changes in dermographism may be observed. , 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, and 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 recorded in areas of demyelination and nerve regeneration, neuromas, as well as in nerve cells of the 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 disruption 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 caused by 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 surviving 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 the disinhibition of neurons and the formation of long-term self-sustaining activity.

Under conditions of insufficient inhibition, synaptic interneuron interactions are facilitated, silent (previously inactive synapses) are activated and nearby hyperactive neurons are united into a single network with self-sustaining activity. These disturbances in the generation and conduction of impulses in peripheral nerves and uncontrolled hyperactivity of central neurons are the pathophysiological basis of sensitivity disorders in the form of paresthesia, dysesthesia, hyperpathia, and allodynia. Sensitivity disorder caused by neuropathic pain due to 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. To diagnose neuropathic pain, a neurological examination is necessary to assess 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 participation of the psyche, consciousness, and thinking in the formation of the sensation of pain. The determining factor in the mechanism of occurrence of psychogenic pain is the disturbed psychological state of a person during depression, hysteria or psychosis. In the clinic, psychogenic pain syndromes are characterized by the presence of severe, prolonged, debilitating pain that is unexplained by any known somatic diseases or damage to the structures of the nervous system. The localization of this pain usually does not correspond to the anatomical features of the tissues or areas of innervation, the defeat of which could be suspected as the cause of the pain. Situations are possible in which somatic damage, including disorders of nerve pathways and centers, can be detected, but the intensity of pain significantly exceeds the degree of damage. As a rule, this is associated with acquired “pain behavior” that develops 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). This state is unconsciously perceived by the patient as a gain, distracts attention from unresolved social and psychological problems, and during the next psychological conflict can be triggered in the form of already habitual “defensive behavior.” With such pain, the function of the suffering organ may be practically unimpaired.

It must be emphasized that chronic pain syndromes are characterized by a combination of pathophysiological processes, when an additional one is connected to the leading basic mechanism, aggravating the clinical picture of pain. For example, “joint” pain can be caused not only by an inflammatory process in the joint and periarticular tissues, but also by damage to peripheral nerves, which requires the use of combination therapy. Typically, more than 1/3 of patients with rheumatoid arthritis are diagnosed with signs of peripheral neuropathy. Neuropathic pain in patients at a rheumatology clinic is often a consequence of nerve damage due to 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 a consequence of tumor invasion of nerve structures, nerve damage during chemotherapy and/or radiation therapy, extensive traumatic surgical interventions, and metastatic damage to nervous system structures. Such combined damage to organ tissue and neuronal formations in cancer patients makes the structure of the pain syndrome complex and requires complex pathogenetically based treatment.

The treatment algorithm for chronic pain must take into account the specific clinical picture, be simple, safe and effective. Medicines must be prescribed for a long period of time and taken strictly according to schedule in individual dosages.

The principles of etiopathogenetic therapy of chronic pain include:

Suppression of the synthesis and release of algogens in damaged tissues;

Limitation of nociceptive afferent impulses from the damaged area to the central nervous system;

Activation of the structures of the antinociceptive system;

Restoration of mechanisms for controlling the excitability of nociceptive neurons;

Elimination of the generation of ectopic impulses in peripheral nerves;

Elimination of painful muscle tension;

Normalization of the patient's psychological state.

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

The most pronounced analgesic effect among drugs that reduce the synthesis of algogens is non-narcotic analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). 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 prostaglandin synthesis. When tissue is damaged under the influence of 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, respectively, into prostaglandins, thromboxane A2 and prostacyclins. 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, the production of which increases during inflammation. Both isoforms of cyclooxygenase are found in peripheral tissues and cells of the central nervous system. Non-narcotic analgesics and most NSAIDs block the activity of both isoforms of cyclooxygenase. To treat pain, both non-selective NSAIDs are used - ibuprofen (Nurofen, Nurofen Plus, etc.), diclofenac, ketoprofen, lornoxicam, and selective COX 2 inhibitors - celecoxib, meloxicam.

Ibuprofen preparations (Nurofen, Nurofen Plus) are the “gold standard” for the treatment of musculoskeletal diseases, which occur in the population with a frequency of approximately 56% and are the second most common among acute pain syndromes after headaches. Nurofen Plus is a combination drug, the effect of which is due to the effects of its constituents ibuprofen and codeine. Ibuprofen - an NSAID, a derivative of phenylpropionic acid - has an analgesic, antipyretic and anti-inflammatory effect by blocking COX. Ibuprofen reduces the concentration of biogenic amines, which have algogenic properties, and thus increases the pain sensitivity threshold of the receptor apparatus. Codeine phosphate is an opium alkaloid of the phenanthrene series, an opioid receptor agonist. Analgesic activity is caused by stimulation 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 tablets.

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

Drugs that limit the flow of nociceptive impulses from the damaged area to the central nervous system

Limiting the entry of nociceptive impulses into the central nervous system is achieved through the use of local anesthetics, which can not only prevent sensitization of nociceptive neurons, but also help normalize microcirculation in the damaged area, reduce inflammatory reactions and improve metabolism. Along with this, local anesthetics, 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 blocking Na + channels on the membrane of nerve fibers and inhibition of the generation of action potentials.

Agents that activate the 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, and non-opioid analgesics of central action are used.

Narcotic analgesics are a class of drugs whose analgesic mechanism 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), agonist-antagonists (butorphanol, nalbuphine) and antagonists (naloxone). Agonists, when 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 as agonists in relation to some, and partial agonists or antagonists in relation to others.

Based on their analgesic activity, narcotic analgesics are divided into weak (codeine, pentazocine), moderate (nalbuphine) and strong (morphine, buprenorphine, fentanyl).

The prescription of narcotic analgesics requires a differentiated approach and is determined by the cause, nature and severity of the pain syndrome. Typically, they are used as highly effective pain relievers for injuries, surgeries, 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, and neuropathic pain. Opioid analgesics began to be prescribed as an alternative to non-narcotic analgesics in cases where they are ineffective or patients have contraindications for their use (nephro- and gastrotoxicity of non-steroidal anti-inflammatory drugs, hepatotoxicity of paracetamol). Extended-release narcotic analgesics (MST-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, when treating 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, the centrally acting analgesic tramadol is used. Tramadol is an opiate receptor agonist and simultaneously inhibits the reuptake of serotonin and norepinephrine at 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 is not classified as a narcotic drug and is prescribed on a prescription form for potent substances. This drug has found its use in the treatment of pain in oncology, surgery, traumatology, rheumatology, neurology, and 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 reduction in side effects from NSAID monotherapy. So, to enhance the analgesic effect, it is possible to combine Nurofen with paracetamol and tramadol for two days.

Antidepressants have found widespread use 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 whose mechanism of action is associated with the blockade of neuronal reuptake of monoamines (serotonin and norepinephrine) in the central nervous system. The greatest analgesic effect was observed with 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 adjuvant analgesics and are usually used in combination with traditional painkillers. Anxiety and depressive disorders accompanying chronic pain syndromes aggravate the pain perception and suffering of patients, which is the basis for the prescription of antidepressants. In addition to their own analgesic effect, antidepressants potentiate the effect of narcotic analgesics, increasing their affinity for opioid receptors.

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

Anticonvulsants or anticonvulsants are the primary treatment for 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 blockade of NA + channels, CA 2+ channels, changes in GABA metabolism and a decrease in glutamate secretion. 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, which primarily block voltage-gated sodium channels (phenytonin, carbamazepine, oxcarbazepine), is achieved by inhibiting ectopic discharges that occur in the damaged nerve and reducing the excitability of central neurons.

Remedies for painful muscle tension

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

Baclofen is an agonist of GABA B receptors and, due to inhibition of interneurons at the spinal level, has a pronounced antispastic and analgesic effect. Baclofen is used for painful muscle spasms in patients with spinal cord and brain damage.

Tolperisone is used as a centrally acting muscle relaxant. The drug, due to its membrane-stabilizing effect and suppression of the secretion of glutamic acid from the central terminals of 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 ensures an effective rupture of connections 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 2 -adrenergic receptors by tizanidine. In addition to muscular spastic conditions caused by damage to the spinal cord and brain, tizanidine is also used for painful muscle strains in patients with pathologies of the musculoskeletal system.

In the treatment of myofascial pain syndromes, local injection into the area of painful muscle compactions of botulinum toxin type A, which blocks the release of acetylcholine at the neuromuscular junction, is also used. The resulting muscle relaxation can provide a long-lasting (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 regions, in painful dysfunction of the temporomandibular joint, and in chronic tension headaches.

Normalization of the patient’s psychological state

To treat psychological problems in patients with chronic pain, it is necessary to use an integrated approach that combines methods of psychotherapy, reflexology, physical therapy and pharmacotherapy. The psychotherapy strategy should be aimed at:

To eliminate internal psychological conflict;

To mobilize the natural capabilities of a person, capable of changing the “pain behavior” that has already become habitual;

To teach patients methods of self-regulation that reduce the intensity of pain.

Depending on the nature of psychopathological symptoms, the severity of motivation and the 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.

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

Therapeutic exercise helps to increase the patient’s level of physical activity, helps normalize his psychological background and social adaptation.

Prescription of medications in patients with psychogenic pain syndromes should be based on the structure of the psychopathological symptom complex. When depressive symptoms dominate, 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 sedative and anti-anxiety effects (amitriptyline, mianserin) are prescribed. In case of predominance of hypochondriacal symptoms, minor antipsychotics (thioridazine, frenolone) are used.

M. L. Kukushkin, Doctor of Medical Sciences, Professor
Research Institute of General Pathology and Pathophysiology of the Russian Academy of Medical Sciences, Moscow

Pain is an important protective biological phenomenon that mobilizes all the functional systems necessary for the survival of the body, allowing it to overcome or avoid the harmful influences that provoked it.
About 90% of all diseases are associated with pain. It is the root basis of medical terms: disease, hospital, patient.
In various regions of the world, from 7 to 64% of the population periodically experience pain, 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, which does not exceed physiologically acceptable limits in intensity) systems.
This balance can be disrupted by short-term but intense nociceptive afferentation or moderate but long-term nociceptive afferentation. Less frequently discussed is the possibility of failure of the antinociceptive system, when physiologically normal nociceptive afferentation begins to be perceived as pain.

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

transient pain
sharp pain
chronic pain

Transient pain is provoked by activation of nociceptive receptors in the skin or other body tissues in the absence of significant tissue damage and disappears until it is completely healed. The function of such pain is determined by the speed of occurrence after stimulation and the speed of elimination, which indicates that there is no danger of damaging effects 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 from external environmental factors in the form of a kind of training of the antinociceptive system to respond adequately, i.e., acquiring pain experience.

Acute pain

Acute pain– a necessary biological adaptive signal about possible (in the case of pain experience), beginning or already occurring damage. The development of acute pain is associated, as a rule, with well-defined painful irritations of superficial or deep tissues and internal organs or dysfunction of the 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 may be:

traumatic
infectious
dismetabolic
inflammatory
and other damage to the peripheral and central nervous system, meninges, short-term neural or muscular syndromes.

Acute pain is divided into:

superficial
deep
visceral
reflected

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

Superficial pain, which occurs when the skin, superficial subcutaneous tissues, and mucous membranes are damaged, is felt as a local sharp, stabbing, burning, pulsating, piercing. It is often accompanied by hyperalgesia and allodynia (a sensation of pain with non-painful stimuli). Deep pain occurs when nociceptors in muscles, tendons, ligaments, joints and bones are irritated. It has a dull, aching character, is less clearly localized than the superficial one.
This or that localization of pain in case of damage to deep tissues is determined by the corresponding spinal segment innervating tendons, muscles, and ligaments. Structures innervated from the same segment can cause the same localization of pain.
And on the contrary, closely located structures innervated by nerves originating from different segments cause pain that differs in localization.
In accordance with the segmental innervation of the damaged tissues, cutaneous hyperalgesia, reflex muscle spasm, and autonomic changes accompanying deep pain are 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 vague, dull, aching in nature.
They can be diffuse, poorly defined topographically. Often accompanied by parasympathetic manifestations: nausea, vomiting, sweating, decreased blood pressure, bradycardia.

Another type of pain that occurs due to pathology of internal organs is referred pain. Referred pain, or the Ged-Zakharyin phenomenon, is projected into dermatomes innervated by the same segments as the deeply located tissues or internal organs involved in the pathological process.
In this case, local hyperalgesia, hyperesthesia, muscle tension, local and diffuse vegetative phenomena occur, the severity of which depends on the intensity and duration of the painful effect.

Intense and prolonged muscle tension (“spasm”) can become an independent cause that increases 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 that lasts 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 tissue. In practice, this may take from 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 a matter of temporal differences as of qualitatively different neurophysiological, psychological and clinical features.
The main thing is that acute pain is always a symptom, and chronic pain can essentially become an independent disease. It is clear that therapeutic tactics for eliminating acute and chronic pain have 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.

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 injury, ischemia and inflammation. In addition to the direct exciting effect on nociceptor membranes, there is an indirect mechanism associated with disruption of local microcirculation.

Increased capillary permeability and venous congestion 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 ongoing release of inflammatory mediators can cause long-term impulses with the development of sensitization of nociceptive neurons and the formation of “secondary hyperalgesia” of the damaged tissue, contributing to the chronicization of the pathological process.

Any peripheral pain is associated with increased 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 sending impulses to the spinal cord and the central nervous system, however, spontaneous electrical activity can be generated at the site of neurogenic inflammation, causing persistent pain.

Such a powerful inducer of pain sensitivity are pro-inflammatory components: bradykins, histamine, neurokinins, nitric oxide, which are usually found at the site 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 the intensity of inflammation and hyperalgesia.
Prostaglandins seem to mediate the involvement of “sleeping” nociceptors in the process of formation of secondary inflammatory hyperalgesia and peripheral sensitization.

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

Hyperalgesia, which is an exaggerated response to a normal painful 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 metabolic products (prostaglandins and leukotrienes), cytokines, etc.

Secondary hyperalgesia is formed due to the involvement of “sleeping” nociceptors in the pathological process.
With adequate relationships between the nociceptive and antinociceptive systems, these multimodal receptors are inactive, but become active following tissue damage (under the influence of histamine, serotonin and bradykinin, released as a result of degranulation of 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 horn of the spinal cord, which increases the excitability of central neurons.
As a result, the peripheral zone of hyperalgesia expands. In this regard, initially subthreshold afferentation from tissues adjacent to the lesion now becomes suprathreshold due to increased excitability (i.e., decreased threshold) of 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 to some extent independent and, from the point of view of therapeutic interventions, 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

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

Principles of pain treatment

Therapy for pain syndromes involves identifying 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 relieving or suppressing acute pain.
Therefore, based on the general principles of pain therapy, first of all the impact is on its source, receptors and peripheral fibers, and then on the dorsal 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 new generation combined analgesics, such as Caffetin ® - one of the drugs that optimally meets these requirements and is intended for the relief of acute pain of moderate and moderate intensity.
The drug contains 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 thermoregulation center in the hypothalamus.
Caffeine stimulates excitation processes in the cerebral cortex (like codeine) and increases the analgesic effect of other components of the drug. The effectiveness of this kind of drugs is confirmed by practice: it is possible to overcome pain, you just need to choose the right medicine.

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 is not recommended.

Treatment of chronic pain syndromes is a more complex task, requiring an integrated approach. 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 class of drugs are anticonvulsants.
The experience available today has proven the need to treat patients with chronic pain in specialized inpatient or outpatient centers with the involvement of neurologists, therapists, anesthesiologists, psychologists, clinical electrophysiologists, physiotherapists, etc.

The basic principle of the treatment of acute pain involves a clinical assessment of the state of the neurophysiological and psychological components of the nociceptive and antinociceptive systems and influence on all levels of organization of this system in order to prevent the chronicization of the pain syndrome, when the dominant clinical component becomes the psychological aspects of the experience of social maladjustment, leading to a deterioration in the quality of life.

Neuropathic pain - diagnosis, rule - “Three Cs”

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

Pain - types of pain, choice of drugs to treat pain

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....

Attention! the information on the site does not constitute a medical diagnosis or a guide to action and is intended for informational purposes only.

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 road from those hospitals you can easily see hundreds of people who were denied even first aid. And pain relief is no exception in this situation. An estimated 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 remains generally unknown. And not only in India. The situation is generally typical for most developing countries.

For any development of medical practice, it is necessary that the initiative comes from a specialist or from the hospital administration. Pain relief does not have the same appeal for them as, for example, cardiovascular surgery. Hospital administrations do not consider this an important task. Infectious disease control, for example, is a public health priority, but pain management is not.

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

First and foremost, the primary goal of a pain management center is to demonstrate the effectiveness of treatment. Unfortunately, sometimes even interested specialists or entire institutions often do not realize the main implications of this area. Most professionals try to treat pain alone, using the methods they are most familiar with and most skilled at. The anesthesiologist uses regional blocks, the acupuncturist tries to treat any pain with acupuncture, and the physical therapist 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 take part in the treatment of pain, and the choice of therapy method should be discussed with the patient or relatives. However, in practice such an ideal model cannot be achieved. Several specialists seeing one patient is a utopian dream that can never be realized, given their busy schedule.

The solution lies in the physician understanding the value of a multidisciplinary approach to pain treatment. The general practitioner must be trained to treat pain as a specialist. Looking at the problem from the patient’s point of view, he must be able to assess 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 consultation with a specialist.

Pain treatment

Since the assessment of pain intensity 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 sensory and emotional components.” Physical pain will inevitably change under the influence of social, emotional and mental factors. Consequently, attempts to treat chronic pain only as a physical component will always be unsuccessful. Every pain management professional needs to keep this in mind. It is always important to establish trusting contact with the patient. “The pain that the patient talks about is always to his detriment.”

The World Health Organization (WHO) Three-Step Ladder (Figure "World Health Organization (WHO) Pain Management Ladder") has revolutionized the treatment of cancer pain worldwide.

It involves the use of analgesics orally by the hour, depending on the duration of action of the drug. At stage I, non-opioid analgesics such as paracetamol or NSAIDs are used. If the effect is insufficient, weak opioids, such as codeine or dextropropoxyphene, are added. If this does not 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 medications by mouth whenever possible. Performing injections over a long period of time is quite uncomfortable and usually causes discomfort for the patient.

♦ When taking drugs orally, the risk of developing allergic reactions, including bronchospasm, is significantly lower.

♦ 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 duration of action of each drug.

I stage of pain treatment

For mild pain of obvious nociceptive nature, an excellent effect is achieved by administering a simple analgesic such as paracetamol if given regularly, say every 4-6 hours. No other analgesic has such a low potential danger that it can be used for a 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 for 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 can be used long-term with success in the treatment of chronic pain.

However, it is necessary to remember the most important side effects:

♦ 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 must be added at stage II.

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

Recommended doses and frequency of prescription of weak opioids for the treatment of pain

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 classified as a strong opioid in some countries)	6-8 hours

Dextropropoxyphene is the most affordable 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 too short a 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 for severe pain.

III stage of pain treatment

If stage II therapy is ineffective, 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 to treat opioid-sensitive pain with careful dosing based on effect, does not cause addiction or respiratory depression. An alarming 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 will be stimulant laxatives such as bisacodyl or senna. Adding liquid paraffin or another emollient to the therapy may be helpful.

♦ 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 fatigued. Some people pay attention to a sharp decrease in appetite, even to the point of anorexia.

♦ Urinary retention is a relatively rare side effect.

♦ Skin itching.

It usually goes away within a few days after starting antihistamine therapy.

When not to use stages I and II

The number of pain management clinics in India can be counted on one hand, which is why we often see patients suffering from sometimes excruciating pain for a long time. In such situations, the concept of the World Health Organization (WHO) pain management ladder obviously needs to be modified. On the one hand, you can try using intravenous boluses of morphine every ten minutes, 1.5 mg, until the intensity of the pain decreases or the patient becomes drowsy. The occurrence of drowsiness while pain persists indicates the presence of pain that is weakly sensitive to opioids. An alternative to intravenous morphine for excruciating pain is to administer 10 mg orally every hour until the desired effect is achieved. It must 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

A paradoxical situation is emerging in India. We supply opium to other countries of the world for medical purposes, while our own patients are forced to suffer for lack of morphine. Responsible in this situation are government agencies that exercise strict, sometimes too strict control over the circulation of narcotic drugs in the country. Currently, the provisions in the drug control system are being simplified. Seven states in India have now simplified controls, making oral morphine significantly more accessible. In other states, a complex licensing system is still a necessity.

Adjuvants for 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. Giving morphine to such a patient only increases his suffering, causing dizziness, fatigue, delirium, or muscle stiffness.

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(a good effect is achieved by prescribing antispasmodic drugs such as dicyclomine or chioscine butyl bromide)

♦ Joint pain(in this situation, the prescription of opioids should be combined with NSAIDs, and in some cases with corticosteroids)

♦ Constipation pain

♦ Neuropathic pain

Basic principles of 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 they begin therapy with them. When administered simultaneously, representatives of these two groups enhance each other's effects.

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. Begin treatment for 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 at synapses.

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

Ketamine hydrochloride, a blocking anesthetic, has also been successfully used in the treatment of neuropathic pain that is 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, physicians may experience significant side effects such as delusions and hallucinations. Amantidine, an antiparkinsonian drug, also being an NMDA antagonist, 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 increased intracranial pressure. They can be prescribed systemically, but with regional administration (for example, epidural) the effect is much better. When administered systemically, dexamethasone is preferred; triamcinolone is the drug of choice for epidural blockade.

Some local procedures may also be used to treat neuropathic pain. With severe cutaneous hyperalgesia, topical application of capsaicin can be very effective. If the nerve proximal to the injury site is intact, the use of transcutaneous electrical nerve stimulation (TENS) will be helpful. For complex regional pain syndrome (CRPS) of the upper extremity, regular stellate ganglion blockade with local anesthetics is recommended.

In the absence of effect from conservative drug therapy, prolonged epidural analgesia or neurolytic procedures can be used. For example, blockade of the celiac plexus for tumors of the upper abdominal cavity. This is also appropriate when the patient comes from afar for examination and selection of therapy. If the effect of standard methods is insufficient, try using alternative adjuvants, for example, epidural administration of alcohol at the thoracic level for thoracic or upper abdominal localization of a malignant tumor.

Basic principles of pain management

The following points may be helpful for a physician who has decided to dedicate himself to helping people suffering from pain:

♦ Identifying the type of pain is the main key to successfully treating it.

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

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

The ability of nervous tissue to undergo anatomical and even genetic changes has been described. Once central pain control is achieved, peripheral treatments (eg, conduction block) 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, they speak of its “somatization.” Quite often this irritates the doctor. Remember that this is not the patient's fault. Certain emotional experiences may also be hidden behind the pain. The doctor will have to figure this out and prescribe appropriate treatment.

♦ If a specific procedure, such as a regional block, is 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 pain treatment service

Any attempt to address pain in a developing country must take into account treatment needs and economic realities. We see that approximately 80% of patients presenting to pain clinics suffer from cancer-related pain. To help such patients, there are two parallel services in most developed countries. 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 need, none of these services are 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:

♦ Your first priority should be the patient's needs.

The needs of 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 help.

♦ The system for providing assistance must be real.

It must be appropriate to 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 something 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 village resident is quite capable of making a decision and choosing a treatment method. Education received 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. They all have their advantages and disadvantages. Always use only necessary products for treatment. A competent choice of the necessary type of therapy is also economically justified.

♦ The shortage of pain treatment products must be filled from non-governmental sources.

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

♦ Volunteers can be a key element in organizing assistance to those suffering from pain.

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

Pain Treatment Experience in Calicut

In Calicut, a small town in the state of Kerala in southern India, we set up a pain management service that can be represented as a kind of pyramid, with the patient at the top, relatives and volunteers below. At the base, supporting them, lies the medical system, represented by state and non-state organizations. The clinic is affiliated to the Government Medical College Hospital and is supported by the Pain and Palliative Care Society, a charitable organization headquartered in Calicut.

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

Over the past eight years, our service has grown significantly to reach an average of 2,000 patients per year at our main clinic located in Calicut. Every day, about 60 people receive the necessary help, and every month about 100-130 new patients make appointments. We are working with doctors from remote areas and non-governmental foundations aimed at creating local branches of the clinic. There are already 27 such clinics operating effectively in various districts of our state. Some even have home visiting programs designed to help seriously ill, non-transportable patients. We estimate that today 15% of those in need of palliative pain treatment in Kerala receive it.

Much has been achieved in these eight years, but there are still around a million people in India who need pain relief. There is no need for expensive drugs and complex sophisticated methods to help them. Morphine made from poppy grown in India, a few other not too expensive drugs, and most importantly, the understanding of health care leaders that a person has the right to freedom from pain - that’s all that is needed for this.

additional literature

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

2. Black RG. 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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! To date, there is no single definition of “chronic pain,” which is primarily due to different sources of the primary pain signal and different mechanisms of pain chronization.

According to the existing time criteria of acute, subacute and chronic pain, as well as the existing definition of pain given by the WHO (i.e. the World Health Organization) and the IASP (International Association for the Study of Pain), the following definition of chronic pain can be given: :

Chronic pain - an unpleasant sensation and emotional experience (defined by 1 - sensory information, 2 - affective reactions and 3 - cognitive activity of the patient) that is associated with actual or potential tissue damage or described in terms of such damage that continues beyond the normal healing period - more than three * (3) months (12 weeks), and which does not respond to conventional medical treatment effective for acute pain.

* note: there is no single time criterion for “chronic pain”; for example, chronic pain, according to the International Association for the Study of Pain, is considered to be pain that continues beyond the normal healing period and lasts at least 3 (three) months, and in accordance with the criteria of the multi-axial nosological system DSM-IV (Diagnostic and Statistical Manual of mental disorders - Guide to the diagnosis and statistics of mental disorders) the concept of “chronic pain” is used to refer to a pain syndrome that lasts more than 6 (six) months.

Based on the definition of chronic pain, its detailed assessment should be based on the patient’s subjective feelings, incl. on affective reactions in response to a painful stimulus and on physiological indicators and characteristics of pain behavior.

! Chronic pain often acquires the status of an independent disease (“pain-disease”), when chronic pain is the only symptom and is observed over a long period of time, and in some cases the cause that caused this pain may not be determined, that is, for chronic pain syndrome, as a rule, there is a lack of direct connection with the organic pathology that caused or could cause pain or the uncertain nature of this connection.

Epidemiology. Chronic pain affects from 2 to 40% of people in the population, on average 15-20%. The majority of patients suffering from chronic pain are elderly patients with several diseases that provoke the development of a pain syndrome of complex etiology.

The source of chronic pain may be any tissue in the body, and the feeling of pain can be maintained through various mechanisms. Modern medical knowledge does not provide a clear understanding of these mechanisms of chronic pain and, as a result, there are no standards for the management of this category of patients.

Among the leading causes of chronic pain in the clinic of nervous diseases, most researchers note pain associated with musculoskeletal problems.

It has now been proven that the leading role in the chronicization of pain (in the formation of chronic pain syndromes) is played by the insufficiency of the antinociceptive system(anti-pain system) due to its congenital inferiority or due to structural (organic) and/or biochemical, including neurotransmitter, pathological changes formed as a result of somatic pathology or pathology of the nervous system (at any level). “Depletion” of the antinociceptive system is facilitated by depression*, anxiety disorders and other chronic psycho-emotional pathological conditions. Physical abuse in childhood has been shown to contribute to the development of chronic pain disorders in adulthood.

* note: many scientists state an obvious close connection between chronic pain and depression; Thus, J. Murray emphasizes that in case of chronic pain one must first of all look for depression; S. Tyrer (1985) provides statistical data on the presence of depressive mental disorders in half of patients suffering from chronic pain; according to S.N. Mosolova, 60% of patients with depression have chronic pain syndromes; some authors are even more specific, believing that in all cases of chronic pain syndrome there is depression, based on the fact that pain is always accompanied by negative emotional experiences and blocks a person’s ability to receive joy and satisfaction.

When studying the anamnesis of patients with chronic pain, it often turns out that in childhood, one of the patients’ close relatives suffered from pain, more often in the same area as the patient. Often the patient himself experienced pain or observed it in emotionally charged situations (for example, the death of a parent from a myocardial infarction with severe pain; headaches leading to a stroke, etc.).

Within the antinociceptive system, the most important neurotransmitters that inhibit pain perception at the supraspinal and spinal levels are serotonin and norepinephrine. Along with them, the opioid, GABAergic and glutamatergic systems, as well as hyperactivity of the hypothalamic-pituitary-adrenal system, participate in the regulation of antinociceptive activity.

Thus (taking into account the above), the pathophysiological basis of “pain” is either a pathological process in the somatic sphere, and/or primary/secondary dysfunction of the structures of the nervous system (peripheral or central); pain is known that is caused only by psychological factors or a combination of the above factors (processes).

Accordingly (according to pathogenetic affiliation), chronic pain can be represented by the following types of pain: (1) nociceptive, (2) neuropathic, (3) psychogenic and (4) mixed (especially in older people).

Nociceptive pain is pain, an obligatory component of which is the activation of peripheral pain receptors under the influence of exogenous and/or endogenous damaging factors. Examples of the most common nociceptive pain are postoperative pain, pain associated with inflammatory joint diseases, back pain, and pain associated with a sports injury. In most cases, the painful stimulus is obvious, the pain is well localized and is easily described by the patient. After cessation of the damaging factor and/or a short course of pain relief with traditional analgesics, nociceptive pain quickly regresses.

! The leading etiological factors of chronic nociceptive pain include arthritis and musculoskeletal pain.

Neuropathic pain is a consequence of damage to the structures of the peripheral and/or central nervous system while the peripheral receptors are intact. In the case of neuropathic pain, the signal is spontaneously generated by the damaged nervous system, overstimulating the structures of the nervous system responsible for pain, which entails the appearance of pain in the absence of a peripheral damaging factor and, accordingly, active peripheral pain receptors. It should be noted that most often the cause of central neuropathic pain is multiple sclerosis, stroke, spondylogenic and post-traumatic myelopathy, and the cause of peripheral neuropathic pain is alcoholic, diabetic, postherpetic polyneuropathy, trigeminal neuralgia, phantom pain, etc.

Neuropathic pain is usually a deep, aching, poorly localized, burning pain that is also characterized by a combination of positive and negative symptoms. Positive symptoms are spontaneous or induced unpleasant sensations such as pain and tingling (paresthesia, dysesthesia, hyperalgesia, and hyperpathia). In turn, negative symptoms are represented by hypoesthesia. One of the most common components of the semiotics of neuropathic pain is the so-called allodynia - the sensation of pain in response to non-painful irritation; Neuropathic pain is characterized by its combination with autonomic symptoms (impaired sweating, swelling, discoloration of the skin) and motor disorders (muscle hypotonia, increased physiological tremor, etc.).

Pathological processes leading to reorganization of the nociceptive system take part in the development and maintenance of neuropathic pain, of which the most studied processes are those associated with the formation of peripheral neuropathic pain:

(1) formation of ectopic(spontaneous) discharges by nerve fibers due to dysfunction of ion channels localized in their membrane;

(2) formation of new pathological synaptic connections afferent axonal terminals in the dorsal horn of the spinal cord - the so-called “springing phenomenon”, which leads to the erroneous perception of non-painful information as painful (the clinical phenomenon of allodynia);

(3) formation of connections by sympathetic postganglionic fibers with afferent conductors of the somatosensory system, as a result of this, signals are exchanged between them, that is, activation of sympathetic (“non-pain”) postganglionic fibers leads to excitation of nociceptors (pain receptors).

Central neuropathic pain is associated with an imbalance of nociceptive and antinociceptive systems as a result of disorganization and damage to antinociceptive structures, which leads to increased and chronic pain.

According to the “accompanying” symptoms (depressive symptoms, dissomnia disorders, asthenia, etc.), chronic neuropathic pain becomes similar to other types of chronic pain.

Psychogenic pain syndromes include: pain caused by emotional factors and muscle tension; pain such as delirium or hallucination in patients with psychosis, which disappears with treatment of the underlying disease; pain due to hypochondria and hysteria that does not have a somatic basis; as well as pain associated with depression that does not precede it and does not have any other cause.

The leading trigger factor for psychogenic pain is psychological conflict, and not damage to somatic and/or visceral organs and/or structures of the somatosensory nervous system.

Clinically, psychogenic pain syndromes are characterized by the presence in patients of pain that is not explained by any known somatic diseases and/or damage to the structures of the nervous system. The localization of pain usually does not correspond to the anatomical features of the tissues or zones of innervation, and the severity of the pain syndrome does not correspond to the identified or suspected damage to the structures of the somatic and/or nervous system (i.e., the intensity of pain significantly exceeds the degree of damage).

Factors contributing to the chronicity and prolongation of both nociceptive and neuropathic pain are: psychosocial factors*; diagnostic and/or therapeutic (i.e., “iatrogenic”) errors that do not lead to timely relief of the pain syndrome, thereby contributing to the formation of sensitization (peripheral and central), which plays an important role in the process of chronicization (prolongation) of pain due to the pain it causes a cascade of secondary neurophysiological and neurochemical transformations that maintain pain.

* note: today it has been proven that the nature, intensity, and duration of pain depend not only on the damage itself, but are also largely determined by unfavorable life situations, as well as social and economic problems (biopsychosocial model of pain).

Psychosocial factors contributing to pain chronicity may include:: the expectation that pain is a manifestation of a “dangerous” disease and can be a cause of disability; emotional stress at the onset of the disease; the belief that pain is related to the conditions of daily work (secondary benefit from the disease); avoidance behavior and reduction of an active position in the strategy for overcoming conflict situations; as well as a tendency towards social dependence and rental attitudes.

Pain is always subjective and each person experiences it differently. However, in order to be able to monitor the dynamics of the pain syndrome, the effectiveness of therapy and other parameters of the treatment process, it is necessary to have ways (and means) to objectify the pain and psycho-emotional state of the patient.

Specific characteristics of pain, indicating poor psychological tolerance of nociceptive stimuli, are the following: pain interferes with the patient’s ability to work, but does not lead to sleep disturbances; the patient vividly describes pain and demonstrates through his behavior that he is sick; experiences pain constantly, while pain sensations are not subject to change; physical activity increases pain, and increased attention and care from others softens it.

In order to unify the patient’s description of pain and objectify the patient’s experiences, questionnaires were created consisting of sets of standard descriptors common to all patients. Most often used McGill questionnaire pain (MPQ - Pain Questionnaire), which contains verbal characteristics of the sensory, affective and motor-motivational components of pain, ranked according to five intensity categories.

Due to the correlation of pain with emotional status, data obtained using quality of life questionnaires and as a result of psychological tests to assess the severity of anxiety and depression are important in choosing optimal therapy.

Scales are used to assess the intensity (severity) of pain and the effectiveness of treatment: a five-point descriptive pain intensity scale, a 10-point quantitative scale, a visual analogue scale (VAS). To differentiate neuropathic pain, there are special tools - the DN4 questionnaire, the LANSS pain scale.

Before moving on to the principles of chronic pain treatment, we list its main clinical signs (summarize):

The duration of the pain is 3 months or more, and the pain lasts most of the day and at least 15* days during the month. The features of chronic pain are that it has a neuropathic monotonous character, periodically intensifying until an attack; may be dull, squeezing, tearing, aching, while patients may refer to it not as pain, but in other terms, for example, “stale”, “cotton” head, “heaviness” in the abdomen, “stuffiness” in the left half of the chest, “unpleasant tickling” in the lumbar region, “something is moving or flowing in the head,” or “difficulty in the passage of blood through the vessels,” etc. (that is, the pain may have a senestopathic color); the localization of pain is always much wider than the patient’s complaint (patients with chronic lower back pain often have headaches, pain in the heart, abdominal pain; upon palpation, such patients experience pain much wider than in the initially presented area); A characteristic feature of chronic pain is the presence of specific “pain behavior,” that is, pain-related behavior.

* note: 15 days is taken from the time criteria for “chronic pain” in DSM-IV (chronic pain corresponds to 6, not 3 months), but this clarification (15 days), as I see it in relation to the problem at hand, is of great importance regardless of the criteria of which guideline the “chronicity” of pain is assessed.

The treatment algorithm for chronic pain can be presented as follows:(N.A. Osipova, G.A. Novikov, 2006): (1) assessment of pain intensity; (2) determining the cause of pain and its pathophysiology; (3) assessment of the patient's physical and mental condition; (3) taking into account comorbid disorders; (4) monitoring the effectiveness of therapy; (5) prevention and correction of side effects

An important component of the success of chronic pain treatment is the use of ( ! ) multimodal and balanced pain management pathways. Combination therapy is most indicated for chronic pain syndrome of complex origin, which has arisen under the influence of several causes. Therefore, pharmacological, non-pharmacological and behavioral techniques (psychotherapy) are used simultaneously or sequentially.

Treatment regimen for chronic pain syndrome(WHO, 1996): 1st stage (mild pain) - non-narcotic analgesics + adjuvant therapy (anticonvulsant, antidepressant, etc.), 2nd stage (moderate pain) - mild opioids(tramadol/codeine or prosidol) + adjuvant therapy , 3rd stage (severe pain) - severe opioids(bupenorphine or morphine sulfate or fentanyl) + adjuvant therapy .

Since chronic pain is “detached” from its primary source, its treatment methods are mainly aimed at activating antinociceptive systems. The pharmacological algorithm for the treatment of chronic pain almost obligately includes antidepressants, priority is given to dual-acting antidepressants (serotonin and norepinephrine reuptake inhibitors, for example, venlafaxine), since these drugs have pronounced analgesic effectiveness (since they significantly increase the activity of the endogenous, pain-suppressing antinociceptive system of the brain) and well tolerated.

However, one of the most important factors when choosing an analgesic is to consider the pathophysiology of pain. Thus, for nociceptive pain, the drugs of choice are NSAIDs; if they are ineffective, narcotic analgesics are prescribed.

In the case of a neuropathic component, anticonvulsants, antidepressants, opioids, and local anesthetics may be used. Long-term use of opioids for the treatment of chronic non-cancer pain is becoming increasingly common. In the early stages of treatment, priority is given to “weak” synthetic opioids*.

* note: pain is not only a negative sensation, but also a process that destroys the regulatory adaptive reactions of the whole organism, thereby contributing to the aggravation of the underlying disease, and therefore it is recognized that, from both the legal and ethical sides, patients with chronic pain syndromes cannot be treated refused to prescribe medications, including opioid analgesics, that provide maximum pain relief; the damage caused to the body by pain itself, in the form of negative emotional experiences, anxiety and depressive disorders, disruption of the visceral systems and the development of secondary immunodeficiency, can be much more serious than the possible side effects of opioids; also long lasting usage opioids are usually accompanied by a reduction in side effects such as nausea, itching and drowsiness

Prescribing opioid analgesics to patients with chronic pain is primarily aimed at improving the quality of life and physical capabilities of a person, therefore, when choosing opioids, it is advisable to use non-invasive forms of drugs and long-acting opioids that provide a lasting analgesic effect. One such treatment is the fentanyl transdermal therapeutic system Durogesic.

It has been proven that in the treatment (relief) of severe chronic pain caused by various pathologies (for example, postherpetic neuralgia, phantom pain, back pain, osteoarthritis, osteoporosis, rheumatoid arthritis, etc.), Durogesic is one of the most effective and safe narcotic analgesics.

(! ) but, despite the above, treatment of chronic pain syndromes with opioids should not be straightforward and should take into account not only the intensity of the pain syndrome, but also the numerous psychological problems associated with pain.

A rational combination of analgesic agents with different mechanisms of action may enhance the effectiveness and/or tolerability of therapy compared with equivalent dosages of each drug having analgesic properties. The combination of paracetamol and a "weak" opioid agent is the most widely used in the world.

In the opinion of some authors, a real breakthrough in the treatment of chronic pain was a fundamentally new class of drugs, superior in effectiveness to many anticonvulsants, antidepressants and narcotic analgesics and without dangerous side effects. This pharmacological class is called SNEPCO (Selective NEuronal Potassium Channel Opener - selective neuronal potassium channel openers), thanks to the selective opening of potassium channels of the neuron, the resting potential of the nerve cell is stabilized - the neuron becomes less excitable, as a result, the excitation of the neuron in response to painful stimuli is inhibited. The first representative of the SNEPCO class is a non-opioid analgesic of central action - Flupirtine (Katadolon).