Nociceptive visceral pain. Nociceptive and antinociceptive systems

Pain syndromes in neurological practice Alexander Moiseevich Vein

1.6. Nociceptive and neuropathic pain

Based on pathophysiological mechanisms, it is proposed to distinguish between nociceptive and neuropathic pain.

nociceptive pain occurs when a tissue-damaging stimulus acts on peripheral pain receptors. The causes of this pain can be a variety of traumatic, infectious, dysmetabolic and other injuries (carcinomatosis, metastases, retroperitoneal neoplasms) that cause activation of peripheral pain receptors. Nociceptive pain is most often acute pain, with all its inherent characteristics (see "Acute and Chronic Pain"). As a rule, the pain stimulus is obvious, the pain is usually well localized and easily described by patients. However, visceral pain, less clearly localized and described, as well as referred pain, is also classified as nociceptive. The appearance of nociceptive pain as a result of a new injury or disease is usually familiar to the patient and is described by him in the context of previous pain sensations. Characteristic of this type of pain is their rapid regression after the cessation of the damaging factor and a short course of treatment with adequate painkillers. However, it should be emphasized that prolonged peripheral irritation can lead to dysfunction of the central nociceptive and antinociceptive systems at the spinal and cerebral levels, which necessitates the fastest and most effective elimination of peripheral pain.

Pain resulting from damage or changes in the somatosensory (peripheral and (or) central) nervous system is referred to as neuropathic. Despite some, in our opinion, the failure of the term "neuropathic", it should be emphasized that we are talking about pain that can occur when there is a violation not only in the peripheral sensory nerves (for example, with neuropathies), but also in the pathology of somatosensory systems in all of its levels from the peripheral nerve to the cerebral cortex. Below is a short list of causes of neuropathic pain depending on the level of the lesion (Table 1). Among these diseases, it should be noted the forms for which the pain syndrome is the most characteristic and occurs more often. These are trigeminal and postherpetic neuralgia, diabetic and alcoholic polyneuropathy, tunnel syndromes, syringobulbia.

Neuropathic pain in its clinical characteristics is much more diverse than nociceptive pain. This is determined by the level, extent, nature, duration of the lesion and many other somatic and psychological factors. In various forms of damage to the nervous system, at different levels and stages of development of the pathological process, the participation of different mechanisms of the genesis of pain may also be different. However, regardless of the level of damage to the nervous system, both peripheral and central pain control mechanisms are always activated.

General characteristics of neuropathic pain are persistent nature, long duration, ineffectiveness of analgesics for its relief, combination with vegetative symptoms. Neuropathic pains are more commonly described as burning, stabbing, aching, or shooting.

Various sensory phenomena are characteristic of neuropathic pain: paresthesia - spontaneous or sensory-induced unusual sensations; dysesthesia - unpleasant spontaneous or induced sensations; neuralgia - pain spreading along one or more nerves; hyperesthesia - hypersensitivity to a normal non-painful stimulus; allodynia - the perception of non-painful irritation as pain; hyperalgesia - an increased pain reaction to a painful stimulus. The last three concepts used to refer to hypersensitivity are combined with the term hyperpathy. One of the types of neuropathic pain is causalgia (sensation of intense burning pain), which occurs most often with complex regional pain syndrome.

Table 1

Levels of damage and causes of neuropathic pain

Damage level	Causes
peripheral nerve	Injuries
	Tunnel Syndromes
	Mononeuropathies and polyneuropathies:
	- diabetes
	- collagenosis
	- alcoholism
	- amyloidosis
	- hypothyroidism
	- uremia
	- isoniazid
Root and posterior horn of the spinal cord	Spine compression (disc, etc.)
	Postherpetic neuralgia
	Trigeminal neuralgia
	Syringomyelia
Conductors of the spinal cord	Compression (trauma, tumor, arteriovenous malformation)
	Multiple sclerosis
	Vitamin B deficiency
	Myelopathy
	Syringomyelia
	Hematomyelia
brain stem	Wallenberg-Zakharchenko syndrome
	Multiple sclerosis
	Tumors
	Syringobulbia
	Tuberculoma
thalamus
	Tumors
	Surgical operations
Bark	Acute cerebrovascular accident (stroke)
	Tumors
	Arteriovenous aneurysms
	Traumatic brain injury

The mechanisms of neuropathic pain in lesions of the peripheral and central parts of the somatosensory system are different. Suggested mechanisms for neuropathic pain in peripheral lesions include: post-denervation hypersensitivity; generation of spontaneous pain impulses from ectopic foci formed during the regeneration of damaged fibers; ephaptic propagation of nerve impulses between demyelinated nerve fibers; increased sensitivity of neuromas of damaged sensory nerves to norepinephrine and certain chemical agents; decrease in antinociceptive control in the posterior horn with damage to thick myelinated fibers. These peripheral changes in the afferent pain stream lead to shifts in the balance of the overlying spinal and cerebral apparatus involved in pain control. At the same time, cognitive and emotional-affective integrative mechanisms of pain perception are obligately switched on.

One of the options for neuropathic pain is central pain. These include pain that occurs when the central nervous system is damaged. With this type of pain, there is a complete, partial or subclinical impairment of sensorimotor sensitivity, most often associated with damage to the spinothalamic pathway at the spinal and (or) cerebral levels. However, it should be emphasized here that a feature of neuropathic pain, both central and peripheral, is the lack of a direct correlation between the degree of neurological sensory deficit and the severity of the pain syndrome.

With damage to the sensory afferent systems of the spinal cord, pain can be localized, unilateral or diffuse bilateral, capturing the area below the level of the lesion. The pains are constant and are burning, stabbing, tearing, sometimes crampial in nature. Against this background, various paroxysmal focal and diffuse pains may occur. An unusual pattern of pain has been described in patients with partial lesions of the spinal cord and its anterior-lateral sections: when pain and temperature stimuli are applied in the zone of loss of sensitivity, the patient feels them in the corresponding zones contralaterally on the healthy side. This phenomenon is called allocheiria ("other hand"). Lermitte's symptom known in practice (paresthesia with elements of dysesthesia during movement in the neck) reflects the increased sensitivity of the spinal cord to mechanical influences in conditions of demyelination of the posterior columns. There are currently no data on similar manifestations in demyelination of the spinothalamic pathways.

Despite the large representation of antinociceptive systems in the brain stem, its damage is rarely accompanied by pain. At the same time, damage to the pons and lateral sections of the medulla oblongata is accompanied by algic manifestations more often than other structures. Central pains of bulbar origin are described in syringobulbia, tuberculoma, tumors of the brain stem, and in multiple sclerosis.

Dejerine and Roussy (1906) described intense unbearable pain as part of the so-called thalamic syndrome (superficial and deep hemianesthesia, sensitive ataxia, moderate hemiplegia, mild choreoathetosis) after infarcts in the region of the thalamic thalamus. The most common cause of central thalamic pain is a vascular lesion of the thalamus (ventroposteriomedial and ventroposteriolateral nuclei). In a special study that analyzed 180 cases of thalamic syndrome in right-handers, it was shown that it occurs twice as often when the right hemisphere is affected (116 cases) than the left hemisphere (64 cases) (Nasreddine Z. S., Saver J. L., 1997). It is curious that the identified predominant right-sided localization is more typical for men. Domestic and foreign studies have shown that thalamic pain often occurs when not only the thalamic thalamus is affected, but also other parts of the afferent somatosensory pathways. The most common cause of these pains are also vascular disorders. Such pains are referred to as “central post-stroke pain”, which occurs in approximately 6-8% of cases of stroke (Wall P. O., Melzack R., 1994; Polushkina N. R., Yakhno N. N., 1995). Thus, the classical thalamic syndrome is one of the options for central post-stroke pain.

The mechanisms of central pain are complex and not fully understood. Recent studies have demonstrated great potential for functional plasticity of the central nervous system in lesions at various levels. The obtained data can be grouped as follows. Damage to the somatosensory system leads to disinhibition and the appearance of spontaneous activity of deafferented central neurons at the spinal and cerebral levels. Changes in the peripheral link of the system (sensory nerve, posterior root) inevitably lead to changes in the activity of thalamic and cortical neurons. The activity of deafferented central neurons changes not only quantitatively, but also qualitatively: under conditions of deafferentation, the activity of some central neurons that were not previously related to the perception of pain begins to be perceived as pain. In addition, under conditions of “blockade” of the ascending pain flow (damage to the somatosensory pathway), afferent projections of neuronal groups at all levels (posterior horns, trunk, thalamus, cortex) are disturbed. At the same time, new ascending projection paths and corresponding receptive fields are formed rather quickly. It is believed that since this process occurs very quickly, it is most likely that spare or “disguised” (inactive in a healthy person) pathways are not formed, but are opened. It may seem that in conditions of pain, these shifts are negative. However, it is postulated that the meaning of such a “desire” for the obligatory preservation of the flow of nociceptive afferentation lies in its necessity for the normal operation of antinociceptive systems. In particular, the insufficient effectiveness of the descending antinociceptive system of the periaqueductal substance, the major raphe nucleus, and the DNIK is associated with damage to the pain afferent systems. The term deafferent pain has been adopted to denote the central pain that occurs when the afferent somatosensory pathways are affected.

Certain pathophysiological features of neuropathic and nociceptive pain were revealed. Special studies have shown that the activity of opioid anti-pain systems was much higher in nociceptive than in neuropathic pain. This is due to the fact that in nociceptive pain the central mechanisms (spinal and cerebral) are not involved in the pathological process, while in neuropathic pain there is their direct suffering. Analysis of works devoted to the study of the effects of destructive (neurotomy, rhizotomy, cordotomy, mesencephalotomy, thalamotomy, leucotomy) and stimulatory methods (TENS, acupuncture, stimulation of the posterior roots, OSV, thalamus) in the treatment of pain syndromes allows us to draw the following conclusion. If procedures for the destruction of nerve pathways, regardless of its level, are most effective in relieving nociceptive pain, then stimulation methods, on the contrary, are more effective in neuropathic pain. However, the leading in the implementation of stimulation procedures are not opiate, but other, not yet specified, mediator systems.

There are differences in drug treatment approaches for nociceptive and neuropathic pain. To relieve nociceptive pain, depending on its intensity, non-narcotic and narcotic analgesics, non-steroidal anti-inflammatory drugs and local anesthetics are used.

In the treatment of neuropathic pain, analgesics are usually ineffective and are not used. Drugs of other pharmacological groups are used.

For the treatment of chronic neuropathic pain, the drugs of choice are antidepressants (tricyclic antidepressants, serotonin reuptake inhibitors) that enhance serotonergic activity (McQuay H. J. et al., 1996). The use of these drugs is due to the insufficiency of the serotonin systems of the brain in many chronic pains, which, as a rule, are combined with depressive disorders.

Some antiepileptic drugs (carbamazepine, diphenin, gabapentin, sodium valproate, lamotrigine, felbamate) are widely used in the treatment of various types of neuropathic pain (Drewes A. M. et al., 1994). The exact mechanism of their analgesic action remains unknown, but it is postulated that the effect of these drugs is associated with: 1) stabilization of neuronal membranes by reducing the activity of voltage-dependent sodium channels; 2) with activation of the GABA system; 3) with inhibition of NMDA receptors (felbamate, lamictal). The development of drugs that selectively block NMDA receptors related to the transmission of pain is one of the priority areas (Weber C., 1998). Currently, NMDA receptor antagonists (ketamine) are not widely used in the treatment of pain syndromes due to numerous adverse side effects associated with the participation of these receptors in the implementation of mental, motor and other functions (Wood T. J., Sloan R., 1997). Certain hopes are associated with the use of drugs from the group of amantadines (used in parkinsonism) for chronic neuropathic pain, which, according to preliminary studies, have a good analgesic effect due to the blockade of NMDA receptors (Eisenberg E., Pud D., 1998).

Anxiolytic drugs and neuroleptics are also used in the treatment of neuropathic pain. Tranquilizers are recommended mainly for severe anxiety disorders, and neuroleptics for hypochondriacal disorders associated with pain. Often these drugs are used in combination with other drugs.

Central muscle relaxants (baclofen, sirdalud) for neuropathic pain are used as drugs that enhance the GABA system of the spinal cord and, along with muscle relaxation, have an analgesic effect. Good results have been obtained in the treatment of postherpetic neuralgia, CRPS, and diabetic polyneuropathy with these agents.

Mexiletine, an analog of lidocaine that affects the operation of sodium-potassium channels in the peripheral nerve, has been proposed in a number of new clinical studies for the treatment of chronic neuropathic pain. It has been shown that at a dose of 600-625 mg per day, mexiletine has a clear analgesic effect in patients with pain syndrome in diabetic and alcoholic polyneuropathy, as well as post-stroke central pain (Wright J. M., Oki J. C., Graves L., 1995; Nishiyama K., Sakuta M., 1995).

Special clinical studies have shown that in neuropathic pain the level of adenosine in the blood and cerebrospinal fluid is significantly reduced compared to the norm, while in nociceptive pain its level is not changed. The analytical effect of adenosine was most pronounced in patients with neuropathic pain (Guieu R., 1996; Sollevi A., 1997). These data indicate insufficient activity of the purine system in neuropathic pain and the adequacy of the use of adenosine in these patients.

One of the directions in the development of effective treatment for neuropathic pain is the study of calcium channel blockers. In preliminary studies of HIV patients suffering from neuropathic pain, a good analgesic effect was obtained with the use of the new calcium channel blocker SNX-111, while emphasizing that the use of opiates in these patients was ineffective.

For citation: Kolokolov O.V., Sitkali I.V., Kolokolova A.M. Nociceptive pain in the practice of a neurologist: diagnostic algorithms, adequacy and safety of therapy. 2015. No. 12. S. 664

Nociceptive pain is commonly referred to as sensations arising in response to irritation of pain receptors by thermal, cold, mechanical and chemical stimuli or caused by inflammation. The term "nociception" was proposed by C.S. Sherrington in order to distinguish between the physiological processes occurring in the nervous system and the subjective experience of pain.

The physiology of nociception includes a complex interaction between the structures of the peripheral and central nervous systems, which provides the perception of pain, the determination of the localization and nature of tissue damage. Usually, nociceptive pain is a protective reaction of the body that promotes the survival of the individual. With inflammation, the adaptive meaning of pain is lost. Therefore, despite the fact that pain during inflammation is nociceptive, some authors distinguish it into an independent form.

The latter is important for developing a strategy and tactics for the relief of nociceptive pain, in particular, determining indications for the use of analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and other drugs. Obviously, for acute pain caused by damage, analgesic therapy that does not have anti-inflammatory properties should be sufficient; for acute or subacute pain due to inflammation, NSAIDs should be most effective. Meanwhile, with inflammatory pain using only NSAIDs, it is not always possible to achieve a quick and complete recovery of the patient, especially in cases where peripheral sensitization develops.

From the point of view of biologists, pain is a psychophysiological reaction of animals and humans to a damaging stimulus that causes organic or functional disorders. The International Association for the Study of Pain (IASP) defines pain as "an unpleasant feeling or emotional sensation associated with actual or potential tissue damage or described in terms of such damage." It is obvious that the sensation of pain can occur not only in case of tissue damage or in conditions of its risk, but also in the absence of it. In the latter case, the determining factor in the occurrence of pain sensation is the presence of mental disorders that change the perception of a person: the pain sensation and the behavior that accompanies it may not correspond to the severity of the damage. The nature, duration and intensity of pain depend on the damage factor and are modified by socio-economic problems. One and the same person can perceive the same pain sensation in different situations in different ways - from insignificant to disabling.

Pain is one of the main reasons people seek medical help. According to N.N. Yakhno et al., in the Russian Federation, patients are most often concerned about back pain (35% of cases), significantly ahead of pain in the pathology of the cervical spine (12%) and diabetic polyneuropathy (11%).

Acute back pain of varying intensity occurs during life in 80-90% of people, in about 20% of cases there is periodic, recurrent, chronic back pain lasting several weeks or more. The occurrence of back pain at the age of 35-45 entails significant socio-economic damage.

From the point of view of neurologists, in order to determine the tactics of treating a patient with back pain, it is extremely important to determine the topical diagnosis and, if possible, establish the etiology of the pain syndrome. Obviously, back pain itself is a non-specific symptom. There are many diseases that manifest as back pain: degenerative-dystrophic changes in the spine, diffuse damage to the connective tissue, diseases of internal organs, etc. This pathology is a multidisciplinary problem. Moreover, often the doctor of the first contact with a patient suffering from pain in the lower back is not a neurologist, but a therapist (in 50% of cases) or an orthopedist (in 33% of cases).

In the vast majority of cases, the causes of back pain are degenerative-dystrophic changes in the spine. An important role is played by inadequate physical activity, overweight, hypothermia, static load, and constitutional features. Instability of vertebral motor segments, changes in intervertebral discs, ligamentous apparatus, muscles, fascia, tendons lead to mechanical irritation of peripheral receptors and the occurrence of nociceptive pain.

As a rule, acute nociceptive pain has clear diagnostic criteria and responds well to treatment with analgesics and NSAIDs. The defeat of the peripheral or central parts of the somatosensory nervous system, which is based on the mechanisms of peripheral and central sensitization, contributes to the formation of neuropathic pain. Such pain is usually chronic, accompanied by anxiety and depression, not relieved by analgesics and NSAIDs, but requires the appointment of antidepressants or anticonvulsants. In addition, socio-cultural factors, personal characteristics, and gender play an important role in the formation of pain sensations. According to numerous studies, complaints of back pain are more often made by women, regardless of age group. Currently, the biopsychosocial concept of pain is generally accepted, which implies, in the treatment of patients, the impact not only on the biological basis of symptoms, but also on the social and psychological elements of the formation of the pain syndrome. In addition, there is associated pain, a typical example of which is back pain.

According to the nature of the course of the pain syndrome, it is customary to distinguish acute (lasting less than 6 weeks), subacute (from 6 to 12 weeks) and chronic (more than 12 weeks) forms.

A simple and practical classification has been internationally endorsed that identifies three types of acute pain in the lower back:

pain associated with the pathology of the spine;
radicular pain;
nonspecific back pain.

Such systematization makes it possible to choose the right tactics for managing a particular patient in accordance with a simple algorithm (Fig. 1). In the majority (85%) of cases, back pain is acute but benign in nature, lasts for several (3–7) days, and is effectively relieved by paracetamol and/or NSAIDs with the addition (if necessary) of muscle relaxants. It is advisable for such patients to provide assistance as soon as possible at the outpatient stage, reducing the time spent on hospitalization and additional examination and without changing the daily activity habitual for a person. At the same time, it is important to observe two conditions: 1) when choosing medicines, use the most effective and safe drugs in effective single and daily doses; 2) when deciding to refuse a detailed examination, understand that the cause of back pain in 15% of cases can be serious diseases of the spine and nervous system.

When determining the tactics of managing a patient, a doctor, having discovered acute pain localized in the lower back, must definitely pay attention to “red flags” - recognizable symptoms and signs that are a manifestation of a serious pathology:

the age of the patient is younger than 20 or older than 55 years;
fresh injury;
increase in pain intensity, lack of dependence of pain intensity on physical activity and horizontal position;
localization of pain in the thoracic spine;
malignant neoplasms in history;
long-term use of corticosteroids;
drug abuse, immunodeficiency, including HIV infection;
systemic diseases;
unexplained weight loss;
severe neurological symptoms (including cauda equina syndrome);
developmental anomalies;
fever of unknown origin.

The most common causes of secondary back pain can be oncological diseases (tumors of the vertebrae, metastatic lesions, multiple myeloma), spinal injuries, inflammatory diseases (tuberculous spondylitis), metabolic disorders (osteoporosis, hyperparathyroidism), diseases of internal organs.

No less important are the “yellow flags” – psychosocial factors that can aggravate the severity and duration of the pain syndrome:

lack of motivation of the patient to active treatment, despite sufficient informing his doctor about the danger of serious complications; passive expectation of treatment results;
behavior inappropriate to the nature of the pain, avoidance of physical activity;
conflicts at work and in the family;
depression, anxiety, post-stress disorder, avoidance of social activity.

The presence of "red" or "yellow" flags dictates the need for additional examination and correction of treatment. For dynamic observation, it is advisable to use pain assessment scales, for example, a visual analogue scale.

It is known that untimely and incomplete relief of acute pain contributes to its chronicity, causes anxiety and depressive disorders in the patient, forms "pain behavior", changes the perception of pain, contributes to the fear of expecting pain, irritability, which requires a different approach to treatment. Therefore, in the absence of "red" or "yellow" flags, it is necessary to focus on finding the fastest and most effective way to relieve pain.

In order to adequately diagnose acute nonspecific pain in the lower back, it is necessary:

to study the anamnesis of the disease and assess the general and neurological status;
if there is anamnesis data indicating a possible serious pathology of the spine or nerve roots, conduct a more detailed neurological examination;
to develop further tactics for managing the patient, determine the topical diagnosis;
pay attention to psychosocial factors in the development of pain, especially in the absence of improvement from treatment;
take into account that the data obtained during radiography, CT and MRI are not always informative for non-specific back pain;
carefully examine patients at a return visit, especially in cases of no improvement in well-being within a few weeks after the start of treatment or deterioration in well-being.

provide the patient with sufficient information about his disease in order to reduce his anxiety about the disease;
remain active and continue normal daily activities, including work, if possible;
prescribe drugs for pain relief with an adequate frequency of administration of drugs (the drug of the first choice is paracetamol, the second is NSAIDs);
prescribe muscle relaxants in a short course as monotherapy or in addition to paracetamol and (or) NSAIDs, if they were not effective enough;
perform manual therapy if the patient's activity is impaired;
use multidisciplinary treatment programs while maintaining subacute pain and disease duration of more than 4-8 weeks.

prescribe bed rest;
prescribe exercise therapy at the onset of the disease;
perform epidural steroid injections;
conduct "schools" for the treatment of acute back pain;
use behavioral therapy;
use traction techniques;
prescribe massage at the onset of the disease;
prescribe transcutaneous electrical nerve stimulation.

Analgesics (paracetamol and opioids) and/or NSAIDs are used to relieve nociceptive back pain. Widely used drugs that reduce the severity of local muscular-tonic syndrome - muscle relaxants.

The problem of choosing NSAIDs is associated with a large number of drugs and conflicting information about their efficacy and safety, as well as comorbidity of patients. The criteria for choosing NSAIDs are high clinical efficacy and safety. Modern principles of prescribing NSAIDs are to use the minimum effective dose of the drug, taking no more than one NSAID at the same time, assessing clinical efficacy after 7–10 days from the start of therapy, and discontinuing the drug immediately after pain relief (Fig. 2). It is necessary to strive for early and complete elimination of pain, active involvement of the patient in the process of treatment and rehabilitation, teaching him methods of preventing exacerbations.

One of the most effective NSAIDs for the treatment of acute nociceptive pain of various etiologies is ketorolac (Ketorol®).

According to the recommendation of the Food and Drug Administration (FDA), ketorolac is intended for the relief of moderate to severe acute pain, in which there is an indication for the appointment of opioids. The drug is not indicated for the treatment of mild and chronic pain. Therapy with ketorolac should always begin with the lowest effective dose, if necessary, the dose may be increased.

In terms of analgesic activity, ketorolac is superior to most NSAIDs, such as diclofenac, ibuprofen, ketoprofen, metamizole sodium, and is comparable to opioids.

A number of randomized clinical trials (RCTs) have proven the high efficacy of ketorolac for the relief of acute pain in surgery, gynecology, traumatology, ophthalmology, and dentistry.

The effectiveness of ketorolac for the relief of migraine attacks has been proven. According to a study by B.W. Friedman et al., which included 120 migraine patients, found ketorolac to be more effective than sodium valproate. The results of a meta-analysis of 8 RCTs presented by E. Taggart et al. proved that ketorolac is more effective than sumatriptan.

As a result of an RCT to study the effectiveness of ketorolac in acute pain caused by degenerative lesions of the articular-ligamentous apparatus, it was found that ketorolac is not inferior in effectiveness to the narcotic analgesic meperidine. A 30% reduction in pain intensity was reported in 63% of patients treated with ketorolac and 67% of patients in the meperidine group.

Information about the opioid-sparing effect of ketorolac deserves attention. G.K. Chow et al. showed that the use of 15-30 mg of ketorolac with a multiplicity of up to 4 r./day can reduce the need for morphine by 2 times.

It is known that the most frequent adverse drug reactions (ADRs) that develop while taking NSAIDs are gastroduodenopathy, which are manifested by erosions and ulcers of the stomach and (or) duodenum, as well as bleeding, perforations and patency disorders of the gastrointestinal tract (GIT). When prescribing ketorolac, the risk of developing NLR from the gastrointestinal tract is higher in elderly patients with a history of ulcers, as well as when administered parenterally at a dose of more than 90 mg / day.

J. Forrest et al. consider that the incidence of NLR when taking ketorolac does not differ in comparison with the use of diclofenac or ketoprofen. At the same time, the risk of developing gastrointestinal bleeding and allergic reactions is statistically significantly lower in patients taking ketorolac compared to patients receiving diclofenac or ketoprofen.

Cardiovascular ADRs while taking NSAIDs are: an increase in the risk of developing myocardial infarction (MI), an increase in blood pressure, a decrease in the effectiveness of antihypertensive drugs, an increase in heart failure. In the work of S.E. Kimmel et al. It has been shown that the incidence of MI in patients receiving ketorolac in the postoperative period is lower than in opioid treatment: MI developed in 0.2% of patients while taking ketorolac and in 0.4% of patients receiving opioids.

Nephrotoxicity while taking ketorolac is reversible and is due to its long-term use. Cases of development of interstitial nephritis, nephrotic syndrome, as well as reversible acute renal failure are described. With an increase in the duration of taking the drug, the risk of nephrotoxic ADR increases: when taking ketorolac for less than 5 days, it was 1.0, more than 5 days - 2.08.

When using ketorolac, it is important to monitor the state of the gastrointestinal tract, cardiovascular system, kidneys and liver. The FDA does not recommend extending ketorolac beyond 5 days due to the increased risk of ADRs.

Thus, ketorolac (Ketorol®) is the drug of choice for the treatment of nociceptive acute pain, in particular, nonspecific pain in the lower back. To increase the effectiveness and safety, ketorolac should be prescribed as early as possible, but in short courses - no more than 5 days.

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Alexey Paramonov

Pain is an ancient mechanism that allows multicellular creatures to fix tissue damage and take measures to protect the body. Emotions play a big role in understanding pain. Even the intensity of ordinary physiological pain largely depends on the emotional perception of a person - someone can hardly tolerate the discomfort from small scratches, and someone can easily treat their teeth without anesthesia. Despite the fact that thousands of studies have been devoted to the study of this phenomenon, there is still no complete understanding of such a relationship. Traditionally, a neurologist determines the pain threshold with a blunt needle, but this method does not give an objective picture.

The pain threshold - its "height" - depends on several factors:

genetic factor - there are "supersensitive" and "insensitive" families;
psychological status - the presence of anxiety, depression and other mental disorders;
previous experience - if the patient has already experienced pain in a similar situation, then next time he will perceive it more sharply;
various diseases - if it increases the pain threshold, then some neurological diseases, on the contrary, lower it.

Important point: All of the above applies only to physiological pain. The complaint "it hurts everywhere" is an example of pathological pain. Such conditions can be either a manifestation of depression and chronic anxiety, or a consequence of problems indirectly related to them (this is the most suitable example).

One of the most important classifications of pain is according to its type. The fact is that each type has specific features and is characteristic of a certain group of pathological conditions. Having established the type of pain, the doctor can reject some of the possible diagnoses and form a reasonable examination plan.

Such a classification divides pain into nociceptive, neuropathic and psychogenic.

nociceptive pain

Typically, nociceptive pain is an acute physiological pain signaling injury or illness. It has a warning function. As a rule, its source is clearly defined - pain in the muscles and bones with a bruise, pain with suppuration (abscess) of the subcutaneous tissue. There is also a visceral variant of nociceptive pain, its source is the internal organs. Despite the fact that visceral pain is not so clearly localized, each organ has its own “pain profile”. Depending on the place and conditions of occurrence, the doctor determines the cause of the pain. So, heart pain can spread to half of the chest, give to the arm, shoulder blade and jaw. In the presence of such symptoms, the doctor will first of all exclude cardiac pathologies.

In addition, the conditions for the occurrence of pain are also important here. If it occurs when walking, and stops during a stop, this is a significant argument in favor of its cardiac origin. If a similar pain occurs when a person lies or sits, but as soon as he gets up, as it passes, the doctor will already think about the esophagus and its inflammation. In any case, nociceptive pain is an important clue when looking for an organic disease (inflammation, tumor, abscess, ulcer).

This type of pain can be described by the words "breaking", "pressing", "bursting", "undulating", or "cramping".

neuropathic pain

Neuropathic pain is associated with damage to the nervous system itself, and with damage at any of its levels - from peripheral nerves to the brain. Such pain is characterized by the absence of obvious disease outside the nervous system - usually it is called "piercing", "cutting", "stabbing", "burning". Often neuropathic pain is combined with sensory, motor and autonomic disorders of the nervous system.

Depending on the damage to the nervous system, pain can manifest itself in the periphery in the form of a burning sensation and a feeling of cold in the legs (with diabetes mellitus, alcoholic disease) and at any level of the spinal column with spread to the chest, anterior abdominal wall and limbs (with radiculitis). In addition, pain can be a sign of damage to one nerve (trigeminal neuralgia, postherpetic neuralgia) or create a complex palette of neurological symptoms if the pathways in the spinal cord and brain are damaged.

Psychogenic pain

Psychogenic pain occurs with various mental disorders (for example, with depression). They can imitate the disease of any organ, but unlike the true disease, complaints are unusually intense and monotonous - the pain can last continuously for many hours, days, months and years. The patient describes such conditions as "painful" and "exhausting". Sometimes the pain can reach such severity that a person is hospitalized with suspected myocardial infarction or acute appendicitis. The exclusion of an organic disease and a multi-month/long-term history of pain is a sign of its psychogenic nature.

How to deal with pain

Initially, nociceptive receptors respond to injury, but after a while, if the irritation does not repeat, the signal from them subsides. At the same time, the antinociceptive system is turned on, which suppresses pain - the brain thus reports that it has received enough information about the event. In the acute phase of injury, if the excitation of nociceptive receptors is excessive, opioid analgesics are best to relieve pain.

2-3 days after the injury, the pain increases again, but this time due to swelling, inflammation and the production of inflammatory substances - prostaglandins. In this case, effective non-steroidal anti-inflammatory drugs - ibuprofen, diclofenac. As the wound heals, if a nerve is involved, neuropathic pain may occur. Neuropathic pain is poorly controlled by non-steroidal media and opioids, the optimal solution for it is anticonvulsants (such as pregabalin) and some antidepressants However, acute and chronic pain almost always report pathology or injury. Chronic pain may be associated with persistent organic disease, such as a growing tumor, but most often the original source is no longer there - the pain maintains itself through the pathological reflex mechanism. An excellent model of self-sustaining chronic pain can be called myofascial pain syndrome - chronic muscle spasm provokes pain, which, in turn, increases muscle spasm.

We often experience pain and every time there is no need to go to the doctor, especially if the pain is already known - we know its cause and are able to cope with it. In the case of new pain, when a person does not understand its nature, or pain accompanied by warning symptoms (nausea, diarrhea, constipation, shortness of breath, fluctuations in pressure and body temperature), you need to contact a specialist. Sometimes, in order to get rid of painful sensations, it is enough to choose an anesthetic and teach a person to avoid the causes of pain, for example, to prevent hypodynamia in myofascial syndrome.

If acute pain has passed quickly, and at the same time you understand its cause, then you do not need to go to the doctor. But keep in mind: sometimes - after a "light" interval - one type of pain can be replaced by another (as happens with appendicitis).

Primarily ibuprofen and paracetamol are available over-the-counter and are used to treat occasional, non-complicated pain (in the head, back, after minor injuries and during painful menstruation). But if these drugs do not help within five days, you should consult a doctor.

The concept of pain is an unpleasant sensory and emotional experience associated with real or perceived tissue damage, and at the same time the reaction of the body, mobilizing various functional systems to protect it from the effects of a pathogenic factor.

Classification Neurophysiological (depending on the mechanism of pain) 1. Nociceptive § Somatic § Visceral 2. Non-nociceptive § Neuropathic § Psychogenic 3. Mixed

Nociceptive pain is pain caused by damage to the musculoskeletal system or internal organs and is directly related to the activation of peripheral pain receptors (nociceptors)

Theories of pain perception A theory authored by M. Frey II. The theory, authored by Goldscheider I.

I. The theory, authored by M. Frey According to her, there are pain receptors in the skin, from which specific afferent pathways to the brain begin. It was shown that when human skin was irritated through metal electrodes, the touch of which was not even felt, “points” were detected, the threshold stimulation of which was perceived as a sharp unbearable pain.

II. Theory by Goldscheider Postulates that any sensory stimulus reaching a certain intensity can cause pain. In other words, there are no specific pain structures, and pain is the result of the summation of thermal, mechanical, and other sensory impulses. Initially called the intensity theory, this theory later became better known as the "pattern" or "summation" theory.

Types of nociceptors. Mechanosensitive and Thermosensitive nociceptors Activated only by intense, tissue-damaging pressure or thermal stimulation. And their effects are mediated by both A-delta and S fibers. Polymodal nociceptors Respond to mechanical and thermal stimuli. A-delta fibers respond to both light touch, pressure, and pain stimuli. Their activity corresponds to the intensity of the stimulus. These fibers also "conduct" information about the nature and location of the painful stimulus.

Types of nerve fibers. Type I (C-fibers) very thin weakly myelinated 0.4-1.1 microns in diameter Type II (A-delta fibers) thin myelinated (1.0-5.0 microns in diameter)

Types of nerve fibers. Connection with various types of pain sensations: Type I (C-fibers) Secondary pain (long-latency) is associated with its afferent stimulation. Type II (A-delta fibers) Primary pain is associated with its afferent stimulation (short-latency)

Substances that cause functional and structural restructuring of nociceptors Plasma and blood cell algogens › › › Bradykinin, kallidin (plasma) Histamine (mast cells) Serotonin, ATP (platelets) Leukotrienes (neutrophils) Interleukin-1, tumor necrosis factor, prostaglandins, nitric oxide ( endothelium, macrophages) C-afferent terminal algogens › Substance P, neurokinin A, calcitonin

ANTINOCICEPTIC NEUROMEDIATORS ØOPIOIDERGIC SYSTEM BETA-ENDORPHIN m-, d MET- and LEU-ENKEPHALIN d- DYNORPHIN k- ENDOMORPHIN m- ØSEROTONIERGIC SYSTEM SEROTONIN 5 HT 1, 5 HT 2, 5 HT 3, 5 HT 4 NORADRENERGIC SYSTEM NORADRENALINE a 2 AAR, a 2 BAR, A 2 car. AR ØGABA-ERGIC SYSTEM GAMBA-Cl(-), GABA-Gi-proteins Ø CANNABINOIDS ANANDAMIDE, 2-ARACHIDONYLGLYCERIN CB 1, CB 2

SOMATOGENIC PAIN SYNDROMES Arise as a result of activation of nociceptors in case of: - injury, ischemia, inflammation, stretching of tissues

Nociceptive (somatogenic) pain I. Somatic Superficial (early, late) II. Visceral Deep Origin Area Skin Connective tissue. Muscles. Bones. Joints. Internal organs Forms of pain Prick, pinch, etc. Muscle cramps, joint pain, etc. Cardialgia, abdominal pain, etc.

I. Somatic pain Superficial pain Early pain is a "bright" in nature, easily localized sensation, which quickly fades with the cessation of the stimulus. It is often followed by a late one with a latency of 0.5 -1.0 sec. Late pain is dull, aching in nature, it is more difficult to localize it, it fades more slowly.

I. Somatic pain Deep pain As a rule, dull, difficult to localize, tends to irradiate into the surrounding tissues.

II. Visceral pain Occurs with rapid and severe stretching of the hollow organs of the abdominal cavity (renal pelvis). Spasms and contractions of internal organs are also painful, especially due to improper circulation (myocardial ischemia).

Pathogenesis of nociceptive pain Damaging factor Primary hyperalgesia in the area of damaged tissue (phenomenon of nociceptor sensitization)

Structures and substrates that cause nociceptive pain. The sequence of stages in the onset of pain The first danger Formation of alkogenic substances Nociceptor Afferent Spinal cord, fiber (A-delta, C) Supraspinal CNS. Stages of information processing Formation and release of harmful substances Transduction and transformation Conduction Central processing

Realization of pain. Sensory-discriminative component Reception, conduction and processing of nociceptive signals Affective (emotional) component Vegetative component Motor component Pain assessment (cognitive component) Expression of pain (psychomotor component)

Physiological purpose of nociceptive pain. Nociceptive pain is a warning signal about the occurrence of disorders (damage) in the body, which opens the way to the recognition and treatment of many diseases.

Types of pain and major groups of antinociceptives*

N. A. Osipova, V. V. Petrova

Federal State Budgetary Institution "Moscow Research Institute of Oncology named after P. A. Herzen" of the Ministry of Health of the Russian Federation, Moscow

The types of pain and basic groups of antinociceptive agents

N. A. Osipova, V V Petrova Moscow Cancer Institute named after P. A. Hertzen, Moscow

The lecture discusses in detail the various types of pain, their sources and localization, the ways of transmitting pain signals, as well as the appropriate methods of protection and pain control. A critical review of drugs intended for the treatment of pain syndrome of various etiologies is presented. Key words: nociceptive pain, somatic pain, visceral pain, hyperalgesia, pain management, antinociceptives.

The lecture is dedicated to different types of pain, its reasons and localization as well as neural ways of pain signal transmitting and corresponding methods of prevention and pain management. The lecture includes a critical overview of drugs and anesthetic agents applied for treating pain of different etiology. Keywords: nociceptive pain, somatic pain, visceral pain, hyperalgesia, pain management, antinociceptive agents

Types of pain

There are two main types of pain: nociceptive and neuropathic, differing in the pathogenetic mechanisms of their formation. Pain caused by trauma, including surgical, is referred to as nociceptive; it should be assessed taking into account the nature, extent, localization of tissue damage, and the time factor.

Nociceptive pain is pain resulting from stimulation of nociceptors in case of damage to the skin, deep tissues, bone structures, internal organs, according to

the mechanisms of afferent impulses and neurotransmitter processes described above. In an intact organism, such pain appears immediately when a local painful stimulus is applied and disappears when it is quickly stopped. However, with regard to surgery, we are talking about a more or less long-term nociceptive effect and often a significant amount of damage to different types of tissues, which creates conditions for the development of inflammation in them and the persistence of pain, the formation and consolidation of pathological chronic pain.

Nociceptive pain is divided into somatic and visceral pain, depending on

Table 1. Types and sources of pain

Types of pain Sources of pain

Nociceptive activation of nociceptors

Somatic In case of damage, inflammation of the skin, soft tissues, muscles, fascia,

tendons, bones, joints

Visceral In case of damage to the membranes of internal cavities, internal organs

(parenchymal and hollow), overstretching or spasm of hollow organs,

vessels; ischemia, inflammation, organ edema

Neuropathic Damage to peripheral or central nerve structures

Psychological component of pain Fear of upcoming pain, unresolved pain, stress, depression,

sleep disturbance

* The third chapter from the book by N. A. Osipova, V. V. Petrova // “Pain in surgery. Means and methods of protection»

localization of damage: somatic tissues (skin, soft tissues, muscles, tendons, joints, bones) or internal organs and tissues - membranes of internal cavities, capsules of internal organs, internal organs, fiber. The neurological mechanisms of somatic and visceral nociceptive pain are not identical, which has not only scientific but also clinical significance (Table 1).

Somatic pain caused by irritation of somatic afferent nociceptors, for example, during mechanical trauma to the skin and underlying tissues, is localized at the site of injury and is well eliminated by traditional analgesics - opioid or non-opioid, depending on the intensity of pain.

Visceral pain has a number of specific differences from somatic pain. The peripheral innervation of different internal organs is functionally different. The receptors of many organs, when activated in response to damage, do not cause conscious perception of the stimulus and a certain sensory sensation, including pain. The central organization of visceral nociceptive mechanisms, compared to the somatic nociceptive system, is characterized by a significantly smaller number of separate sensory pathways. . Visceral receptors are involved in the formation of sensory sensations, including pain, and are interconnected with autonomic regulation. The afferent innervation of the internal organs also contains indifferent ("silent") fibers, which can become active when the organ is damaged and inflamed. This type of receptor is involved in the formation of chronic visceral pain, supports long-term activation of spinal reflexes, impaired autonomic regulation and the function of internal organs. Damage and inflammation of the internal organs disrupts the normal pattern of their motility and secretion, which in turn dramatically changes the environment around

receptors and leads to their activation, the subsequent development of sensitization and visceral hyperalgesia.

In this case, signals can be transmitted from the damaged organ to other organs (the so-called viscero-visceral hyperalgesia) or to the projection zones of somatic tissues (viscerosomatic hyperalgesia). Thus, in different visceral algogenic situations, visceral hyperalgesia can take different forms (Table 2).

Hyperalgesia in the damaged organ is considered as primary, and viscerosomatic and viscero-visceral - as secondary, since it does not occur in the zone of primary damage.

Sources of visceral pain can be: the formation and accumulation of pain substances in the damaged organ (kinins, prostaglandins, hydroxytryptamine, histamine, etc.), abnormal stretching or contraction of the smooth muscles of hollow organs, stretching of the capsule of the parenchymal organ (liver, spleen), anoxia of smooth muscles , traction or compression of ligaments, vessels; zones of organ necrosis (pancreas, myocardium), inflammatory processes. Many of these factors operate during intracavitary surgical interventions, which determines their higher trauma and greater risk of postoperative dysfunctions and complications compared to non-cavitary operations. In order to reduce this risk, research is being conducted to improve the methods of anesthetic protection, and minimally invasive thoraco-, laparoscopic and other endoscopic operations are being actively developed and implemented. Prolonged stimulation of visceral receptors is accompanied by excitation of the corresponding spinal neurons and the involvement of spinal cord somatic neurons in this process (the so-called viscerosomatic interaction). These mechanisms are mediated by IMOL receptors and are responsible for

Table 2. Types of hyperalgesia in visceral pain

Type of hyperalgesia Localization

1. Visceral The organ itself during its nociceptive stimulation or inflammation

2. Viscerosomatic Zones of somatic tissues where visceral hyperalgesia is projected

3. Viscero-visceral Transfer of hyperalgesia from the originally involved internal organ to others whose segmental afferent innervation partially overlaps

development of visceral hyperalgesia and peripheral sensitization.

Neuropathic pain (NPP) is a specific and most severe manifestation of pain associated with damage and disease of the peripheral or central somatosensory nervous system. It develops as a result of traumatic, toxic, ischemic damage to nerve formations and is characterized by abnormal sensory sensations that exacerbate this pathological pain. NPB can be burning, stabbing, spontaneous, paroxysmal, can be provoked by non-painful stimuli, such as movement, touch (the so-called allodynia), spreads radially from the area of nerve damage. The main pathophysiological mechanisms of NPB include peripheral and central sensitization (increased excitability of peripheral and spinal nociceptive structures), spontaneous ectopic activity of damaged nerves, sympathetically enhanced pain due to the release of norepinephrine, which stimulates nerve endings with the involvement of neighboring neurons in the process of excitation, while reducing the descending inhibitory control of these processes with a variety of severe sensory disorders. The most severe manifestation of NPB is a phantom pain syndrome after amputation of the limbs, associated with the intersection of all the nerves of the limb (deafferentation) and the formation of overexcitation of nociceptive structures. NPB is often resistant to conventional analgesic therapy, persists for a long time, and does not decrease over time. The mechanisms of NPB are being refined in experimental studies. It is clear that there is a violation of the processes of sensory information, an increase in excitability (sensitization) of nociceptive structures, and inhibitory control suffers.

The development of special approaches to the prevention and treatment of NPB, aimed at reducing the overexcitation of the peripheral and central structures of the sensory nervous system, continues. Depending on the etiology of clinical manifestations, NSAIDs, local applications of ointments and patches with local anesthetics, glucocorticoids or NSAIDs are used; muscle relaxants

central action, serotonin and norepinephrine reuptake inhibitors, antidepressants, anticonvulsants. The latter seem to be the most promising in relation to severe neuropathic pain syndromes associated with trauma to nerve structures.

Persistent/inflammatory pain in the area of surgical or other invasive impact develops with continued stimulation of nociceptors by mediators of pain and inflammation, if these processes are not controlled by preventive and therapeutic agents. Unresolved persistent postoperative pain is the basis of chronic postoperative pain syndrome. Its different types are described: postthoracotomy, postmastectomy, posthysterectomy, postherniotomy, etc. . Such persistent pain, according to these authors, can last days, weeks, months, years. The research conducted in the world indicates the high importance of the problem of persistent postoperative pain and its prevention. The development of such pain can contribute to many factors acting before, during and after surgery. Among the preoperative factors - the psychosocial status of the patient, the initial pain at the site of the upcoming intervention, other concomitant pain syndromes; among intraoperative - surgical access, the degree of invasiveness of the intervention and damage to the nervous structures; among postoperative ones - unresolved postoperative pain, means of its treatment and doses, relapse of the disease (malignant tumor, hernia, etc.), quality of patient management (observation, consultations with the attending physician or in the pain clinic, the use of special testing methods, etc.).

The frequent combination of different types of pain should be taken into account. In surgery during intracavitary operations, activation of the mechanisms of both somatic and visceral pain is inevitable. During noncavitary and intracavitary operations accompanied by trauma, intersection of nerves, plexuses, conditions are created for the development of manifestations of neuropathic pain against the background of somatic and visceral pain, followed by its chronicity.

The importance of the psychological component associated with pain or

expected pain, which is especially important for surgical clinics. The psychological state of the patient significantly affects his pain reactivity and, conversely, the presence of pain is accompanied by negative emotional reactions, violates the stability of the psychological status. There is an objective justification for this. For example, in patients entering the operating table without premedication (i.e., in a state of psycho-emotional stress), a sensory study recorded a significant change in reactions to an electrocutaneous stimulus compared to the initial ones: the pain threshold is significantly reduced (pain is aggravated), or, conversely, , increases (i.e., pain reactivity decreases). At the same time, important patterns were revealed when comparing the analgesic effect of a standard dose of fentanyl 0.005 mg/kg in people with reduced and increased emotional pain response. In patients with emotional stress analgesia, fentanyl caused a significant increase in pain thresholds - 4 times, and in patients with high emotional pain reactivity, pain thresholds did not change significantly, remaining low. The same study established the leading role of benzodiazepines in eliminating preoperative emotional stress and achieving an optimal background for the manifestation of the analgesic effect of the opioid.

Along with this, the so-called. psychosomatic pain syndromes associated with psycho-emotional overloads of various kinds, as well as somatopsychological ones that develop against the background of organic diseases (for example, oncological ones), when the psychological component makes a significant contribution to the processing and modulation of pain information, intensifying pain, so that a mixed picture is ultimately formed. somatic, somatopsychological and psychosomatic pain.

A correct assessment of the type of pain and its intensity, depending on the nature, location and extent of the surgical intervention, underlies the appointment of means for its adequate therapy. Even more important is the preventive pathogenetic approach to the planned selection of specific antinociceptive agents for various types of surgical interventions in order to avoid inadequate anesthetic protection (AP), the formation of a strong

postoperative pain syndrome and its chronicity.

The main groups of means of protection against pain associated with tissue injury

In the surgical clinic, specialists have to deal with acute pain of various types of intensity and duration, which affect the definition of tactics not only for pain relief, but also for the management of the patient as a whole. So, in case of unexpected, sudden onset of acute pain associated with the underlying (surgical) or concomitant disease (perforation of a hollow abdominal organ, acute attack of hepatic / renal colic, angina pectoris, etc.), anesthesia is started by establishing the cause of the pain and tactics for its elimination ( surgical treatment or drug therapy for the disease that caused the pain).

In elective surgery, we are talking about predictable pain, when the time of the surgical injury, the location of the intervention, the estimated zones and extent of damage to tissues and nerve structures are known. At the same time, the approach to protecting the patient from pain, in contrast to pain relief in case of actually developed acute pain, should be preventive, aimed at inhibiting the processes of triggering nociceptive mechanisms before the onset of surgical trauma.

The construction of an adequate AZ of a patient in surgery is based on the multilevel neurotransmitter mechanisms of nociception discussed above. Research on the improvement of AZ in various areas of surgery is actively conducted in the world, and, along with the well-known traditional means of systemic and regional anesthesia and analgesia, in recent years the significance of a number of special antinociceptive agents that increase the effectiveness and reduce the disadvantages of traditional agents has been substantiated.

Means, the use of which is advisable to protect the patient from pain at all stages of surgical treatment, are divided primarily into 2 main groups:

Systemic antinociceptives

actions;

local antinociceptives

(regional) action.

Systemic antinociceptives

These drugs suppress one or another pain mechanism by entering the systemic circulation through various routes of administration (intravenous, intramuscular, subcutaneous, inhaled, orally, rectally, transdermally, transmucosally) and acting on the appropriate targets. Numerous systemic drugs include drugs of various pharmacological groups that differ in certain antinociceptive mechanisms and properties. Their targets can be peripheral receptors, segmental or central nociceptive structures, including the cerebral cortex.

There are different classifications of systemic antinociceptives based on their chemical structure, mechanism of action, clinical effects, and taking into account the rules for their medical use (controlled and uncontrolled). These classifications include different groups of analgesic drugs, the main pharmacological property of which is the elimination or reduction of pain. However, in anesthesiology, in addition to analgesics proper, other systemic agents with antinociceptive properties are used, which belong to other pharmacological groups and play an equally important role in the patient's anesthetic protection.

Their action is focused on different parts of the nociceptive system and the mechanisms of the formation of acute pain associated with surgery.

Antinociceptive agents of local (regional) action (local anesthetics)

Unlike systemic agents, local anesthetics have their effect when they are applied directly to the nervous structures of different levels (terminal endings, nerve fibers, trunks, plexuses, structures of the spinal cord). Depending on this, local anesthesia can be superficial, infiltration, conduction, regional or neuraxial (spinal, epidural). Local anesthetics block the generation and propagation of action potentials in nerve tissues mainly by inhibiting the function of Na+ channels in axonal membranes. Na+ channels are specific receptors for local anesthetic molecules. Different sensitivity of nerves to local anesthetics can be manifested by a clinically significant difference in the blockade of somatic sensory innervation, motor and preganglionic sympathetic fibers, which, along with the desired sensory blockade, may be accompanied by additional side effects.

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Dear Colleagues!

At the beginning of this year, the publishing house "Medical Information Agency" published a monograph by the famous specialist in the field of treatment of postoperative pain, long-term head of the department of anesthesiology and resuscitation of the Research Institute of Oncology named after P. A. Herzen, Honored Scientist of the Russian Federation, Professor N. A. Osipova " Pain in surgery. Means and methods of protection, co-authored with a senior researcher, Ph.D. V. V. Petrova.

The lack of specialized literature on postoperative pain relief makes this event particularly significant. We can say that since the appearance in Russia of M. Ferrante's monograph "Postoperative Pain", Russian anesthesiologists have not received such a complete guide to combat pain in patients who have undergone various surgical interventions. The authors present the most up-to-date data on the anatomical and physiological basis of pain, molecular genetic and neurotransmitter mechanisms of its formation.

The book provides a critical analysis of various non-opioid and opioid analgesics, non-analgesics that affect IMEL receptors. Particular attention is paid to the neuropathic component of postoperative pain, the significance of which is rarely taken into account by practitioners. Of great interest is the chapter devoted to the prevention of phantom pain syndrome, an issue that is considered unresolved all over the world, but is successfully solved within the walls of the Research Institute of Oncology. P. A. Herzen. Separate chapters are devoted to the issues of perioperative analgesia in the orthopedic clinic, anesthetic protection of patients during intracavitary operations, interventions on the head and neck. In this issue of the journal, we present one of the chapters of the monograph by N. A. Osipova and V. V. Petrova, which presents the types of pain and the main groups of means of protection against pain in surgery.

We hope that it will interest you, and you will want to read the monograph as a whole.

Chief editor, prof. A. M. Ovechkin