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 has been proposed to distinguish between nociceptive and neuropathic pain.

Nociceptive pain occurs when a tissue-damaging irritant 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), causing 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 painful stimulus is obvious, the pain is usually well localized and is easily described by patients. However, visceral pain, less clearly localized and described, as well as referred pain are 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. It should, however, be emphasized that long-term peripheral irritation can lead to dysfunction of the central nociceptive and antinociceptive systems at the spinal and cerebral levels, which necessitates the need for 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 classified as neuropathic. Despite some, in our opinion, inadequacy 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 with pathology of the somatosensory systems in all 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 damage (Table 1). Among the above diseases, it should be noted the forms for which pain is the most characteristic and occurs more often. These are trigeminal and postherpetic neuralgia, diabetic and alcoholic polyneuropathy, tunnel syndromes, syringobulbia.

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

The general characteristics of neuropathic pain are persistent, long duration, ineffectiveness of analgesics to relieve it, and combination with autonomic symptoms. Neuropathic pain is more often described as burning, stabbing, aching, or shooting.

Neuropathic pain is characterized by various sensory phenomena: paresthesia - spontaneous or induced unusual sensory sensations; dysesthesia - unpleasant spontaneous or evoked sensations; neuralgia - pain spreading along the course of one or more nerves; hyperesthesia - increased sensitivity to a common non-painful stimulus; allodynia - the perception of non-painful irritation as painful; hyperalgesia - increased pain response to a painful stimulus. The last three concepts used to denote hypersensitivity are combined under the term hyperpathy. One type of neuropathic pain is causalgia (a feeling of intense burning pain), which most often occurs with complex regional pain syndrome.

Table 1

Levels of involvement and causes of neuropathic pain

Damage level	Causes
Peripheral nerve	Injuries
	Tunnel syndromes
	Mononeuropathy and polyneuropathy:
	- diabetes
	- collagenoses
	- alcoholism
	- amyloidosis
	- hypothyroidism
	- uremia
	- isoniazid
Root and dorsal horn of the spinal cord	Root compression (disc, etc.)
	Postherpetic neuralgia
	Trigeminal neuralgia
	Syringomyelia
Spinal cord conductors	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. Proposed mechanisms of 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 some chemical agents; decreased antinociceptive control in the dorsal horn with damage to thick myelinated fibers. These peripheral changes in the afferent pain flow lead to shifts in the balance of the overlying spinal and cerebral apparatus involved in pain control. In this case, cognitive and emotional-affective integrative mechanisms of pain perception are obligately activated.

One type of 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 absence of a direct correlation between the degree of neurological sensory deficit and the severity of the pain syndrome.

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

Despite the large representation of antinociceptive systems in the brain stem, its damage is rarely accompanied by pain. In this case, damage to the pons and lateral parts of the medulla oblongata is more often than other structures accompanied by algic manifestations. Central pain of bulbar origin has been described in syringobulbia, tuberculoma, brain stem tumors, and multiple sclerosis.

Dejerine and Roussy (1906) described intense unbearable pain within the so-called thalamic syndrome (superficial and deep hemianesthesia, sensory ataxia, moderate hemiplegia, mild choreoathetosis) after infarctions in the area of the optic thalamus. The most common cause of central thalamic pain is vascular damage to the thalamus (its 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 with damage to the right hemisphere (116 cases) than to the left (64 cases) (Nasreddine Z. S., Saver J. L., 1997). It is curious that the revealed predominant right-sided localization is more typical for men. Domestic and foreign studies have shown that pain of a thalamic nature often occurs when not only the thalamus opticus is affected, but also other areas of the afferent somatosensory pathways. The most common cause of these pains is also vascular disorders. Such pain is designated by the term “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 classic thalamic syndrome is one of the variants of central post-stroke pain.

The mechanisms of central pain are complex and not fully understood. Research in recent years has demonstrated the great potential for functional plasticity of the central nervous system with 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 part of the system (sensory nerve, dorsal 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 (dorsal horns, trunk, thalamus, cortex) are disrupted. In this case, new ascending projection pathways and corresponding receptive fields are formed quite quickly. It is believed that since this process occurs very quickly, it is likely that spare or “camouflaged” (inactive in a healthy person) pathways are opened, rather than formed. It may seem that in conditions of pain these shifts are negative. However, it is postulated that the meaning of such a “striving” for the obligatory preservation of the flow of nociceptive afferentation lies in its necessity for the normal functioning of antinociceptive systems. In particular, the insufficient effectiveness of the descending antinociceptive system of the periaqueductal substance, the raphe nuclei magnus, and the DNIK is associated with damage to the pain afferentation systems. The term deafferentation pain is adopted to designate central pain that occurs when afferent somatosensory pathways are damaged.

Certain pathophysiological features of neuropathic and nociceptive pain have been identified. Special studies have demonstrated that the activity of opioid anti-pain systems was much higher in nociceptive than in neuropathic pain. This is due to the fact that with nociceptive pain, central mechanisms (spinal and cerebral) are not involved in the pathological process, whereas with neuropathic pain there is direct suffering. Analysis of works devoted to the study of the effects of destructive (neurotomy, rhizotomy, cordotomy, mesencephalotomy, thalamotomy, leukotomy) and stimulation methods (TENS, acupuncture, stimulation of the dorsal 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 for neuropathic pain. However, the leading ones in the implementation of stimulation procedures are not opiate, but other, not yet specified, mediator systems.

There are differences in the approaches to drug treatment of 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), which 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, usually 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 pain transmission is one of the priority areas (Weber S., 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 amantadine group (used for parkinsonism) for chronic neuropathic pain, which, according to preliminary studies, have a good analgesic effect due to blockade of NMDA receptors (Eisenberg E., Pud D., 1998).

Anxiolytic drugs and antipsychotics are also used in the treatment of neuropathic pain. Tranquilizers are recommended mainly for severe anxiety disorders, and antipsychotics 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 drugs.

A number of new clinical studies have proposed the drug mexiletine, an analogue of lidocaine, which affects the functioning of sodium-potassium channels in the peripheral nerve, 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 due to 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 adenosine use 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, good analgesic effect was obtained with the new calcium channel blocker SNX-111, while emphasizing that the use of opiates in these patients was ineffective.

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

Nociceptive pain is usually called sensations that occur 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 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, providing the perception of pain, determining the location and nature of tissue damage. Typically, 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 as an independent form.

The latter is important for developing strategies and tactics for the relief of nociceptive pain, in particular determining indications for the use of analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), muscle relaxants and other drugs. Obviously, for acute pain caused by injury, treatment with analgesics that do not have anti-inflammatory properties should be sufficient; for acute or subacute pain resulting from inflammation, NSAIDs should be most effective. Meanwhile, with inflammatory pain, using only NSAIDs 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 it 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 the presence 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 the sensation of pain is the presence of mental disorders that change a person’s perception: the sensation of pain and the accompanying behavior may not correspond to the severity of the injury. The nature, duration and intensity of pain depend on the factor of injury and are modified by socio-economic problems. 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 why people seek medical help. According to N.N. Yakhno et al., in the Russian Federation, patients are most often bothered by back pain (35% of cases), significantly ahead of pain due to 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 approximately 20% of cases, periodic, recurrent, chronic back pain lasting several weeks or more is observed. The onset of back pain at the age of 35–45 years entails significant socio-economic damage.

From the point of view of neurologists, in order to determine the treatment tactics for 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 nonspecific symptom. There are many diseases that manifest as back pain: degenerative-dystrophic changes in the spine, diffuse damage to connective tissue, diseases of internal organs, etc. This pathology is a multidisciplinary problem. Moreover, often the doctor of first contact with a patient suffering from pain in the lower back is not a neurologist, but a therapist (in 50% of calls) 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, excess body weight, hypothermia, static load, and constitutional features. Instability of the vertebral motor segments, changes in the intervertebral discs, ligaments, muscles, fascia, and 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. Damage to 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, and is not relieved by analgesics and NSAIDs, but requires the use of antidepressants or anticonvulsants. In addition, sociocultural factors, personal characteristics, and gender play an important role in the formation of pain. According to numerous studies, women are more likely to complain of back pain, regardless of age group. Currently, the biopsychosocial concept of pain is generally accepted, which involves treating patients by influencing not only the biological basis of symptoms, but also 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 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 received international approval, which distinguishes three types of acute pain in the lower back:

pain associated with spinal pathology;
radicular pain;
nonspecific pain in the back.

Such systematization allows you 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, lasts several (3-7) days and is effectively relieved with paracetamol and (or) NSAIDs with the addition (if necessary) of muscle relaxants. It is advisable to provide assistance to such patients as soon as possible on an outpatient basis, reducing the time spent on hospitalization and additional examination and without changing the person’s usual daily activities. In this case, it is important to observe two conditions: 1) when choosing medications, 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 for managing a patient, the doctor, having discovered acute pain localized in the lower back, must pay attention to the “red flags” - recognizable symptoms and signs that are a manifestation of a serious pathology:

the patient's age 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;
history of malignant neoplasms;
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 (vertebral tumors, metastatic lesions, multiple myeloma), spinal injuries, inflammatory diseases (tuberculous spondylitis), metabolic disorders (osteoporosis, hyperparathyroidism), diseases of internal organs.

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

lack of motivation of the patient for active treatment, despite sufficient information by the doctor about the danger of serious complications; passive waiting for 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 disorders, avoidance of social activities.

The presence of “red” or “yellow” flags dictates the need for additional examination and treatment adjustment. For dynamic monitoring, 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 the appearance of anxiety and depressive disorders in the patient, forms “pain behavior”, changes the perception of pain, contributes to the emergence of fear of anticipation of pain, irritability, which requires a different approach to treatment. Therefore, in the absence of “red” or “yellow” flags, it is necessary to focus specifically 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:

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

provide the patient with sufficient information about his disease in order to reduce his anxiety about the disease;
stay active and continue normal daily activities, including work if possible;
prescribe medications for pain relief with an adequate frequency of drug administration (the drug of 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 are not effective enough;
carry out manual therapy if the patient’s activity is impaired;
use multidisciplinary treatment programs if subacute pain persists and the disease lasts more than 4–8 weeks.

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

To relieve nociceptive back pain, analgesics (paracetamol and opioids) and (or) NSAIDs are used. Drugs are widely used to 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 effectiveness and safety, as well as patient comorbidity. The criteria for choosing NSAIDs are high clinical efficacy and safety. Modern principles of prescribing NSAIDs include using the minimum effective dose of the drug, taking no more than one NSAID at a time, assessing clinical effectiveness 7–10 days after the start of therapy, and discontinuing the drug immediately after pain relief (Fig. 2). One should strive for early and complete elimination of pain, active involvement of the patient in the process of treatment and rehabilitation, and training in 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 Food and Drug Administration (FDA), ketorolac is indicated for the treatment of moderate to severe acute pain for which opioids are indicated. The drug is not indicated for the treatment of mild and chronic pain. Ketorolac therapy should always begin with the minimum effective dose, with the dose possibly increasing if necessary.

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 effectiveness of ketorolac for the relief of acute pain in surgery, gynecology, traumatology, ophthalmology, and dentistry.

Ketorolac has been proven effective in relieving migraine attacks. According to the results of the study by B.W. Friedman et al., which included 120 patients with migraine, ketorolac was more effective compared to 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 studying 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 receiving ketorolac and 67% of patients in the meperidine group.

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

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

J. Forrest et al. believe that the incidence of ADRs when taking ketorolac is no different compared to using 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: increased risk of myocardial infarction (MI), increased blood pressure, decreased effectiveness of antihypertensive drugs, increased 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 when treated with opioids: MI developed in 0.2% of patients receiving ketorolac and in 0.4% of patients receiving opioids.

Nephrotoxicity caused by ketorolac is reversible and is due to its long-term use. Cases of the development of interstitial nephritis, nephrotic syndrome, as well as reversible acute renal failure have been described. As the duration of taking the drug increases, the risk of nephrotoxic ADRs increases: when taking ketorolac for less than 5 days, it was 1.0, and for more than 5 days – 2.08.

When using ketorolac, it is important to monitor the condition of the gastrointestinal tract, cardiovascular system, kidneys and liver. The FDA does not recommend extending the course of treatment with 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.

Literature

Pain: a guide for students and doctors / Ed. N.N. Yakhno. M., 2010. 304 p.
Danilov A., Danilov A. Pain management. Biopsychosocial approach. M., 2012. 582 p.
ACPA resource guide to chronic pain medication & treatment. 2015. 135 p.
Chow G.K. et al. Prospective double-blend study of effect of ketorolac administration after laparoscopic urologic surgery // J. Endourol. 2001. Vol. 15. P. 171-174.
European guidelines for the management of acute nonspecific low back pain in primary care // Eur. Spine J. 2006. Vol. 15 (Suppl. 2). P. 169-191.
Feldman H.I. et al. Perenteral ketorolac: the risk for acute renal failure // Ann. Intern. Med. 1997. Vol. 127. P. 493-494.
Forrest J. et al. Ketorolac, diclofenac and ketoprofen are equally safe for pain relief after major surgery // Brit. J. Anaesth. 2002. Vol. 88. P. 227-233.
Franceschi F. et al. Acetaminophen plus codeine compared to ketorolac in polytrauma patients // Eur. Rev. Med. Pharmacol. Sci. 2010. Vol. 14. P. 629-634.
Friedman B.W. et al. Randomized trial of IV valproate vs metoclopramide vs ketorolac for acute migraine // Neurol. 2014. Vol. 82(11). P. 976-983.
Kimmel S.E. et al. Parenteral ketorolac and risk of myocardial infarction // Pharm. Drug. Saf. 2002. Vol. 11. P. 113-119.
Lee A. et al. Effects of nonsteroidal anti-inflammatory drugs on post-operative renal function in adults with normal renal function // Cochrane Database Syst. Rev. 2007(2). CD002765.
Rainer T.H. Cost effectiveness analysis of intravenous ketorolac and morphine for treating pain after limb injury: double blind randomized controlled trial // BMJ. 2000. Vol. 321. P.1247-1251.
Roche Laboratories. Toradol iv, im, and oral (ketorolac tromethamine) prescribing information. Nutley // NJ. 2002. Sep.
Stephens D.M. et al. Is Ketorolac Safe to Use in Plastic Surgery? A Critical Review // Aesthet. Surg. J. 2015. Mar 29. pii: sjv005.
Taggart E. et al. Ketorolac in the treatment of acute migraine: a systematic review // Headache. 2013. Vol. 53(2). P. 277-287.
Traversa G. et al. Cohort study of hepatotoxicity associated with nimesulide and other non-steroidal anti-inflammatory drugs // BMJ. 2003. Vol. 327 (7405). P.18-22.
US Food and Drug Administration. Proposed NSAID Package Insert Labeling Template 1. From the FDA website. Accessed 10 Oct. 2005.
Veenema K., Leahey N., Schneider S. Ketorolac versus meperidine: ED treatment of severe musculoskeletal low back pain // Am. J. Emerg. Med. 2000. Vol. 18(4). P. 40404-40407.

Alexey Paramonov

Pain is an ancient mechanism that allows multicellular creatures to detect 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 a person’s emotional perception - some people can hardly bear the discomfort of minor scratches, while others can easily have their teeth treated without anesthesia. Despite the fact that thousands of studies have been devoted to the study of this phenomenon, there is no complete understanding of such a relationship yet. Traditionally, a neurologist determines the pain threshold using a blunt needle, but this method does not provide an objective picture.

The pain threshold - its “height” - depends on several factors:

genetic factor - there are “hypersensitive” 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 acutely;
various diseases - if it increases the pain threshold, then some neurological diseases, on the contrary, lower it.

Important point: everything said above concerns only 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 (the most suitable example is this).

One of the most important classifications of pain is by its type. The fact is that each type has specific signs 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 formulate a reasonable examination plan.

This classification divides pain into nociceptive, neuropathic and psychogenic.

Nociceptive pain

Typically, nociceptive pain is an acute physiological pain that signals injury or illness. It has a warning function. As a rule, its source is clearly defined - pain in the muscles and bones during a bruise, pain during suppuration (abscess) of the subcutaneous tissue. There is also a visceral version 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 location and conditions of occurrence, the doctor determines the cause of the pain. Thus, heart pain can spread to half of the chest, radiating to the arm, shoulder blade and jaw. If such symptoms are present, the doctor will first rule out cardiac pathologies.

In addition, the conditions under which pain occurs are also important. If it occurs when walking and stops while stopping, this is a significant argument in favor of its cardiac origin. If similar pain occurs when a person is lying or sitting, but as soon as he gets up, it goes away - the doctor will think about the esophagus and its inflammation. In any case, nociceptive pain is an important clue when searching for an organic disease (inflammation, tumor, abscess, ulcer).

This type of pain can be described as “aching”, “pressing”, “bursting”, “wavy” or “cramping”.

Neuropathic pain

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

Depending on the damage to the nervous system, pain can manifest itself on the periphery in the form of a burning sensation and a feeling of cold in the legs (with diabetes, alcoholism) and at any level of the spinal column with spread to the chest, the anterior wall of the abdomen 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 in various mental disorders (for example, depression). They can imitate a disease of any organ, but unlike a true disease, the complaints are characterized by unusual intensity and monotony - the pain can last continuously for many hours, days, months and years. The patient describes this condition as “excruciating” and “debilitating”. Sometimes painful sensations can reach such severity that a person is hospitalized with suspicion of 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 cope with pain

Initially, nociceptive receptors react to injury, but after a while, if the irritation is not repeated, the signal from them subsides. At the same time, the antinociceptive system is activated, 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 best relieve pain.

2-3 days after the injury, the pain intensifies again, but this time due to swelling, inflammation and the production of inflammatory substances - prostaglandins. In this case, effective nonsteroidal 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 indicate pathology or injury. Chronic pain can be associated with a persistent organic disease, such as a growing tumor, but most often the original source is no longer there - the pain maintains itself through the mechanism of a pathological reflex. An excellent model of self-sustaining chronic pain is myofascial pain syndrome - chronic muscle spasm provokes pain, which, in turn, increases muscle spasm.

We often experience pain and there is no need to see a doctor every time, especially if the pain is already known - we know its cause and know how to cope with it. In case of new pain, when a person does not understand its nature, or pain accompanied by alarming symptoms (nausea, diarrhea, constipation, shortness of breath, fluctuations in pressure and body temperature), you need to consult a specialist. Sometimes, in order to get rid of painful sensations, it is enough to select a painkiller and teach the person to avoid the causes of pain, for example, to avoid physical inactivity in case of myofascial syndrome.

If the acute pain goes away quickly, and you understand its cause, then there is no need to go to the doctor. But keep in mind: sometimes - after a “bright” interval - one type of pain can be replaced by another (as happens with appendicitis).

First of all, ibuprofen and paracetamol are available over-the-counter; they allow you to cope with occasional pain that does not threaten complications (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 a reaction of the body that mobilizes various functional systems to protect it from the effects of a pathogenic factor.

Classification Neurophysiological (depending on the pain mechanism) 1. Nociceptive § somatic § visceral 2. Non-noceptive § 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 Theory, authored by M. Frey II. Theory, authored by Goldscheider I.

I. Theory, authored by M. Frey According to it, the skin contains pain receptors, 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 identified, the threshold stimulation of which was perceived as sharp, unbearable pain.

II. The theory, authored by Goldscheider, postulates that any sensory stimulus reaching a certain intensity can cause pain. In other words, there are no specific pain structures, but pain is the result of the summation of thermal, mechanical and other sensory impulses. Initially called intensity theory, this theory later became better known as "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 Fibers. Polymodal nociceptors Respond to mechanical and thermal stimuli. A-delta fibers respond to both light touch, pressure, and painful stimuli. Their activity corresponds to the intensity of the stimulus. These fibers also “conduct” information about the nature and localization of the pain stimulus.

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

Types of nerve fibers. Connection with different 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 (short-latency) is associated with its afferent stimulation

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

NEUROMEDIATORS ANTINOCICEPTIVE Ø OPIOIDERGIC SYSTEM BETA-ENDORPHIN m-, d MET- and LEU-ENKEPHALIN d- DYNORPHIN k- ENDOMORPHIN m- Ø SEROTONINERGIC SYSTEM SEROTONIN 5 HT 1, 5 HT 2, 5 HT 3, 5 HT 4 ØNORADRENERGIC SYSTEM NORADRENALINE a 2 AAR, a 2 BAR, A 2 car. AR Ø GABAergic SYSTEM GAMKA-Cl(-), GABA-Gi-proteins Ø CANNABINOIDS ANANDAMIDE, 2 -ARACHIDONYLGLYCEROL SV 1, SV 2

SOMATOGENIC PAIN SYNDROMES Occur as a result of activation of nociceptors during: - trauma, ischemia, inflammation, tissue stretching

Nocicetative (somatogenic) pain I. Somatic Superficial (early, late) II. Visceral Deep Area of origin Skin Connective tissue. Muscles. Bones. Joints. Internal organs Forms of pain Injection, pinch, etc. Muscle cramp, 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 away 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 and aching in nature, it is more difficult to localize, and it fades more slowly.

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

II. Visceral pain Occurs with rapid and strong 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 (nociceptor sensitization phenomenon) Repeated stimulation of C-afferents Secondary hyperalgesia (progressive increase in the excitability of nociceptive neurons - the “inflating” phenomenon)

Structures and substrates causing nociceptive pain. Sequence of stages of pain occurrence 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 Carrying out Central processing

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

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

Types of pain and main groups of antinociceptive drugs*

N. A. Osipova, V. V. Petrova

FSBI "Moscow Research Oncology Institute named after P. A. Herzen" of the Ministry of Health of the Russian Federation, Moscow

The types of pain and basic groups of antinoticeptic agents

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

The lecture discusses in detail the different types of pain, their sources and localization, the ways in which pain signals are transmitted, as well as appropriate methods of protecting and combating pain. A critical review of drugs intended for the treatment of pain syndromes of various etiologies is presented. Key words: nociceptive pain, somatic pain, visceral pain, hyperalgesia, pain treatment, antinociceptive drugs.

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, which differ in the pathogenetic mechanisms of their formation. Pain caused by trauma, including surgery, is classified as nociceptive; it should be assessed taking into account the nature, extent, localization of tissue damage, and the time factor.

Nociceptive pain is pain that occurs due to stimulation of nociceptors when the skin, deep tissues, bone structures, internal organs are damaged, according to

the mechanisms of afferent impulse and neurotransmitter processes described above. In an intact organism, such pain appears immediately upon application of a local painful stimulus and goes away when it quickly stops. However, in relation to surgery, we are talking about a more or less long-term nociceptive effect and often a significant scale of damage to various types of tissues, which creates conditions for the development of inflammation and persistence of pain in them, the formation and consolidation of pathological chronic pain.

Nociceptive pain is divided into somatic and visceral depending on

Table 1. Types and sources of pain

Types of pain Sources of pain

Nociceptive Activation of nociceptors

Somatic For damage, inflammation of the skin, soft tissues, muscles, fascia,

tendons, bones, joints

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

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

vessels; ischemia, inflammation, organ edema

Neuropathic Damage to peripheral or central nervous 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 - the 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 the pain.

Visceral pain has a number of specific differences from somatic pain. The peripheral innervation of different internal organs is functionally different. 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 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, disruption of autonomic regulation and function of internal organs. Damage and inflammation of 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 (so-called visceral-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 a damaged organ is considered primary, and viscerosomatic and viscero-visceral - as secondary, since it does not occur in the area of primary damage.

Sources of visceral pain can be: the formation and accumulation of painful 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 a parenchymal organ (liver, spleen), anoxia of smooth muscles , traction or compression of ligaments, blood vessels; areas of organ necrosis (pancreas, myocardium), inflammatory processes. Many of these factors operate during intracavitary surgical interventions, which determines their higher morbidity and greater risk of postoperative dysfunction and complications compared to non-cavitary operations. In order to reduce this risk, research is being conducted to improve methods of anesthetic protection, 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 somatic neurons of the spinal cord in this process (the so-called viscerosomatic interaction). These mechanisms are mediated by YMOL receptors and are responsible for

Table 2. Types of hyperalgesia for 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 initially involved internal organ to others whose segmental afferent innervation is partially overlapped

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 aggravate this pathological pain. NPP can be burning, stabbing, spontaneously occurring, paroxysmal, can be provoked by non-painful stimuli, such as movement, touch (the so-called allodynia), and spreads radially from the area of nerve damage. The main pathophysiological mechanisms of NPP 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 excitation process while simultaneously reducing descending inhibitory control of these processes with a variety of severe sensory disorders. The most severe manifestation of NPP is phantom pain syndrome after limb amputation, associated with the intersection of all nerves of the limb (deafferentation) and the formation of overexcitation of nociceptive structures. NBP is often resistant to treatment with conventional analgesics, persists for a long time and does not decrease over time. The mechanisms of NBP are being clarified in experimental studies. It is clear that there is a disruption in sensory information processes, increased excitability (sensitization) of nociceptive structures, and inhibitory control suffers.

The development of special approaches to the prevention and treatment of NSP continues, aimed at reducing overexcitation of the peripheral and central structures of the sensory nervous system. 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 action 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 for days, weeks, months, years. Research conducted around the world indicates the high importance of the problem of persistent postoperative pain and its prevention. Many factors before, during, and after surgery can contribute to the development of such pain. Preoperative factors include the patient’s psychosocial status, initial pain at the site of the upcoming intervention, and other associated pain syndromes; among intraoperative ones - surgical approach, the degree of invasiveness of the intervention and damage to nerve structures; among postoperative ones - unresolved postoperative pain, means of its treatment and dose, relapse of the disease (malignant tumor, hernia, etc.), quality of patient management (observation, consultations with the attending physician or in the pain clinic, 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 both somatic and visceral pain mechanisms is inevitable. During non-cavitary 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 with its subsequent chronicization.

The importance of the psychological component accompanying pain or

expected pain, which is especially important for surgical clinics. The psychological state of the patient significantly influences his pain reactivity and, conversely, the presence of pain is accompanied by negative emotional reactions and disrupts 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 sensorometric study records a significant change in reactions to an electrodermal stimulus compared to the initial ones: the pain threshold is significantly reduced (pain worsens), or, on the contrary , increases (i.e. pain reactivity decreases). At the same time, important patterns were identified when comparing the analgesic effect of a standard dose of fentanyl 0.005 mg/kg in people with a reduced and increased emotional pain reaction. 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, developing against the background of organic diseases (for example, cancer), when the psychological component makes a significant contribution to the processing and modulation of pain information, increasing pain, so that a mixed picture is ultimately formed somatic, somatopsychological and psychosomatic pain.

Correct assessment of the type of pain and its intensity, depending on the nature, location and extent of the surgical intervention, underlies the prescription of adequate therapy. Even more important is a 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 a surgical clinic, specialists have to deal with acute pain of various types of intensity and duration, which influence the determination of tactics not only for pain relief, but also for the management of the patient as a whole. So, in the case of unexpected, sudden acute pain associated with the main (surgical) or concomitant disease (perforation of a hollow abdominal organ, acute attack of hepatic/renal colic, angina pectoris, etc.), anesthesia begins by establishing the cause of the pain and tactics for its elimination ( surgical treatment or drug therapy for the disease causing the pain).

In planned surgery we are talking about predictable pain, when the time of surgical trauma, the localization of the intervention, the expected zones and the extent of damage to tissues and nerve structures are known. In this case, the approach to protecting the patient from pain, in contrast to pain relief for acute pain that has actually developed, should be preventive, aimed at inhibiting the processes of triggering nociceptive mechanisms before the onset of surgical trauma.

The basis for constructing an adequate AZ for a patient in surgery is the multilevel neurotransmitter mechanisms of nociception discussed above. Research to improve AD in various areas of surgery is actively being conducted in the world, and, along with the well-known traditional means of systemic and regional anesthesia and analgesia, in recent years the importance of a number of special antinociceptive agents has been substantiated, increasing the effectiveness and reducing the disadvantages of traditional means.

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 antinociceptive agents

actions;

Local antinociceptive agents

(regional) action.

Systemic antinociceptive agents

These drugs suppress one or another mechanism of pain, entering the systemic circulation through different routes of administration (intravenously, intramuscularly, subcutaneously, by inhalation, orally, rectally, transdermally, transmucosally) and acting on the corresponding targets. Numerous agents of systemic action include drugs from a variety of pharmacological groups, differing in certain antinociceptive mechanisms and properties. Their targets may be peripheral receptors, segmental or central nociceptive structures, including the cerebral cortex.

There are different classifications of systemic antinociceptive drugs based on their chemical structure, mechanism of action, clinical effects, and also 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 easing of pain. However, in anesthesiology, in addition to the analgesic drugs themselves, other systemic agents with antinociceptive properties are used, which belong to other pharmacological groups and play an equally important role in the anesthetic protection of the patient.

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

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

In contrast to systemic agents, local anesthetics exert their effect when they are applied directly to nerve structures at different levels (terminal endings, nerve fibers, trunks, plexuses, spinal cord structures). 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 may 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.

Literature

1. Babayan E. A., Gaevsky A. V., Bardin E. V. Legal aspects of the circulation of narcotic, psychotropic, potent, toxic substances and procurers. M.: MCFR; 2000.

2. Yakhno N.N. ed. Pain: A Guide for Doctors and Students. M.: MEDpress; 2009.

3. Danilov A. B., Davydov O. S. Neuropathic pain. M.: BORGES; 2007: 56-57.

4. Kukushkin M. L., Tabeeva T. R., Podchufarova E. V. Pain syndrome: pathophysiology, clinic, treatment. P/ed. N. N. Yakhno M.: IMApress; 2011.

5. Yakhno N. N., Alekseeva V. V., Podchufarova E. V., Kukushkina M. L. eds. Neuropathic pain: clinical observations. M.; 2009.

6. Osipova N. A., Abuzarova G. R. Neuropathic pain in oncology. M.; 2006.

7. Osipova N. A., Abuzarova G. R., Petrova V. V. Principles of using analgesics for acute and chronic pain. Clinical recommendations. M.; 2011.

8. Osipova N. A. Assessment of the effect of narcotic, analgesic and psychotropic drugs in clinical anesthesiology. M.: Medicine; 1988: 137-179.

9. Smolnikov P.V. Pain: Choice of protection. Formulary. M.: MAIK. "Science/Interperiodics", 2001.

10. Striebel H. V. Therapy of chronic pain. Practical guide. M.: GEOTAR-Media, 2005; 26-29.

11. Basbaum A., Bushell M. C., Devor M. Pain: Basic Mechanisms. In: Pain 2005-an Updated Review. Refresher Course Syllabus. Ed. Justins D.M. IASP Press. Seattle. 2005; 3-12.

12. Basbaum A., Bushell M. C., Devor M. Pain: Basic Mechanisms. In: Pain 2008-an Updated Review. Refresher Course Syllabus. IASP Press. Seattle. 2008; 3-10.

13. Butterworth J. F., Strichartz G. R. Molecular mechanisms of local anesthesia: a review. Anaesthesiology, 1990; 72: 711-73.

14. Cervero F. Mechanisms of visceral pain. In: Pain 2002-an Updated Review. Refresher Course Syllabus. IASP Press. Seattle. 2002; 403-411.

15. Dickenson A. H., Bee L. A. Neurobiological mechanisms of neuropathic pain and its treatment. Pain 2008-an Updated Review. Refresher Course Syllabus. Eds Castro-Lopes, Raja S., Shmelz M. IASP Press. Seattle. 2008; 277-286.

16. Giamberardino M. A. Urogenital pain and phenomena of viscero-visceral hyperalgesia. Pain 2002-an Updated Review. Refresher Course Syllabus. Ed. Giamberardino M.A. IASP Press. Seattle. 2002; 413-422.

17. Hansson P. T. Neuropathic pain: definition, diagnostic criteria, clinical phenomenology and differential diagnostic issues. Pain 2008-an Updated Review. Refresher Course Syllabus. Eds Castro-Lopes, Raja S., Shmelz M. IASP Press. Seattle. 2008; 271-276.

18. Jensen T. S. Management of neuropathic pain. Pain 2008-an Updated Review. Refresher Course Syllabus. Eds CastroLopes, Raja S., Shmelz M. IASP Press. Seattle. 2008; 287295.

19. Kehlet H. Persistent postsurgical pain: surgical risk factors and strategies for prevention. In: Pain 2008-an Updated Review. Refresher Course Syllabus. IASP Press. Seattle. 2008; 153-158.

20. McMahon C. B. Neuropathic pain mechanisms In: Pain 2002-an Updated Review. Refresher Course Syllabus. IASP Press. Seattle. 2002; 155-163.

21. Veering B. Focus on adjuvants in regional anesthesia. Euroanaesthesia.Vienna, Austria. Refresher Course Lectures. ESA 2005; 217-221.

Dear Colleagues!

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

The shortage of specialized literature on postoperative pain management makes this event especially significant. It can be said that since the appearance in Russia of M. Ferrante’s monograph “Postoperative Pain,” Russian anesthesiologists have not received such comprehensive guidance on dealing with pain in patients who have undergone various surgical interventions. The authors present the most modern 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, drugs that are not related to analgesics, but have an effect on NMEL receptors. Particular attention is paid to the neuropathic component of postoperative pain, the significance of which is rarely taken into account by practicing physicians. Of great interest is the chapter devoted to the prevention of phantom pain syndrome, an issue that is considered unresolved throughout the world, but is being successfully resolved within the walls of the Oncology Research Institute. P. A. Herzen. Separate chapters are devoted to the issues of perioperative analgesia in an orthopedic clinic, anesthetic protection of patients during intracavitary operations, and 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, presenting the types of pain and the main groups of means of protecting against pain in surgery.

We hope that it will interest you and that you will want to familiarize yourself with the monograph as a whole.

Editor-in-chief, prof. A. M. Ovechkin