Types and mechanisms of pain syndromes. Pathophysiology of pain (VolgGMU). Pathophysiological mechanisms of somatogenic pain syndromes

Pathophysiology of pain

Pain is the most common symptom affecting millions of people around the world. The treatment and elimination of pain is one of the most important tasks, which in its importance can be compared with life-saving measures. What is pain?

The International Association for the Study of Pain Expert Group defined pain as follows: "Pain is an unpleasant sensation and emotional experience associated with or described in terms of actual or potential tissue damage."

Pain is a kind of psycho-physiological state of a person that occurs as a result of exposure to super-strong or destructive stimuli and causes functional or organic disorders in the body. The very word "disease" is directly related to the concept of "pain". Pain should be considered as a stress factor, which, with the participation of the sympathetic nervous system and the "hypothalamus-pituitary-adrenal cortex" system, mobilizes functional and metabolic systems. These systems protect the body from the effects of a pathogenic factor. Pain includes such components as consciousness, sensation, motivation, emotions, as well as autonomic, somatic and behavioral reactions. Nociceptive and antinociceptive mechanisms underlie the sensation and awareness of pain.

The system of transmission and perception of the pain signal belongs to the nociceptive system. Pain signals cause the inclusion of adaptive reactions aimed at eliminating the stimulus or the pain itself. Under normal conditions, pain plays the role of the most important physiological mechanism. If the strength of the stimulus is great and its action continues for a long time, then the adaptation processes are disturbed, and the physiological pain turns from a protective mechanism into a pathological mechanism.

The main manifestations of pain

1. Motor (withdrawal of a limb during a burn, injection)

2. Vegetative (increased blood pressure, shortness of breath, tachycardia)

3. Somatogenic (pain in the muscles, bones, joints)

4. Metabolic (activation of metabolism)

The trigger mechanism for these manifestations is the activation of the neuroendocrine and, first of all, the sympathetic nervous system.

Types of pain

Under the action of a damaging factor, a person can feel two types of pain. With an acute injury (for example, when hitting a sharp object, an injection), local severe pain occurs. This is primary, epicritic pain. The structural basis of such pain is myelinated A δ fibers and the spinothalamocortical pathway. They provide precise localization and intensity of pain. After 1-2 seconds epicritic pain disappears. It is replaced by a slowly increasing in intensity and long-lasting secondary, protopathic pain. Its occurrence is associated with slowly conducting non-myelinated C-fibers and the spinocortical system.

Pain classification

1. According to the localization of damage, there are:

a) somatic superficial pain

b) somatic deep pain

c) visceral pain

d) neuropathic pain

e) central pain

2. According to the flow and time parameters, they distinguish:

a) severe pain

b) chronic pain

3. According to the mismatch of pain with the site of injury, the following are distinguished:

a) referred pain

b) projected pain

By pathogenesis

a) somatogenic (nociceptive) pain - irritation of receptors during trauma, inflammation, ischemia (postoperative and post-traumatic pain syndromes)

b) neurogenic pain - in case of damage to the structures of the peripheral or central nervous system (trigeminal neuralgia, phantom pain, thalamic pain, causalgia)

c) psychogenic pain - the action of psychological and social factors

Superficial Deep

Somatic Visceral Acute Chronic

By location Downstream

Neuropathic Central

By pathogenesis When pain does not match

with damage site

PAIN

Somato- Neuro- Psycho- Reflected Projected

gene gene gene pain pain

Let's dwell on the characteristics of some types of pain

Visceral pain is pain localized in the internal organs. It is diffuse in nature, often not amenable to clear localization, accompanied by oppression, depression, changes in the function of the autonomic nervous system. Pain in diseases of the internal organs occurs as a result of: 1) blood flow disorders (atherosclerotic changes in blood vessels, embolism, thrombosis); 2) spasm of smooth muscles of internal organs (with gastric ulcer, cholecystitis); 3) stretching of the walls of hollow organs (gall bladder, renal pelvis, ureter); 4) inflammatory changes in organs and tissues.

Pain impulses from the internal organs are transmitted to the central nervous system through the thin fibers of the sympathetic and parasympathetic nervous systems. Visceral pain is often accompanied by the formation of referred pain. Such pain occurs in organs and tissues that do not have morphological changes, and is due to the involvement of the nervous system in the pathological process. Such pain can occur with heart disease (angina pectoris). When the diaphragm is damaged, pain appears in the back of the head or shoulder blade. Diseases of the stomach, liver and gallbladder are sometimes accompanied by toothache.

A special kind of pain is phantom pain - pain localized by patients in the missing limb. The nerve fibers cut during the operation can get into the scars, pressed by the healing tissues. In this case, impulses from damaged nerve endings through the nerve trunks and posterior roots enter the spinal cord, where the pain perception apparatus in the missing limb is preserved, reach the visual tubercles and the cerebral cortex. In the central nervous system, a dominant focus of excitation occurs. Thin nerve conductors play an important role in the development of these pains.

Pain etiology

1. Extreme irritant

Any stimulus (sound, light, pressure, temperature factor) can cause a pain reaction if its strength exceeds the sensitivity threshold of the receptors. An important role in the development of the pain effect is played by chemical factors (acids, alkalis), biologically active substances (histamine, bradykinin, serotonin, acetylcholine), potassium and hydrogen ions. Excitation of receptors also occurs during their prolonged irritation (for example, during chronic inflammatory processes), the action of tissue decay products (during tumor decay), compression of the nerve by a scar or bone tissue

2. Pain conditions

Violation of the skin, fatigue and insomnia, cold increase pain. Pain is influenced by the time of day. It was noted that at night, pain in the stomach, gallbladder, renal pelvis, pain in the area of the hands and fingers, pain in case of damage to the vessels of the extremities intensify. Hypoxic processes in nerve conductors and tissues contribute to increased pain.

3. Reactivity of the body

Inhibitory processes in the central nervous system prevent the development of pain, excitation of the central nervous system enhances the pain effect. Increase the pain of fear, anxiety, self-doubt. If the body expects the application of painful irritation, then the feeling of pain decreases. It is noted that in diabetes mellitus, pain in the trigeminal nerve, which innervates the oral cavity (jaws, gums, teeth), increases. A similar effect is observed with insufficient function of the gonads.

With age, the nature of the pain changes. Pain becomes chronic, the pain becomes dull, which is due to atherosclerotic changes in blood vessels and impaired microcirculation in tissues and organs.

Modern theories of pain

There are currently two theories to explain pain:

1. Theory of "gateway" control (theory of control of afferent input)

2. Theory of generator and systemic mechanisms of pain

Gate control theory

According to this theory, in the system of afferent input to the spinal cord, in particular, in the posterior horns of the spinal cord, there is a mechanism for controlling the passage of nociceptive impulses. It has been established that somatic and visceral pain is associated with impulses in slow-conducting fibers of small diameter belonging to the group A δ (myelinated) and C (non-myelinated). Thick myelin fibers (A  and A ) serve as conductors of tactile and deep sensitivity. Control over the passage of pain impulses is carried out by inhibitory neurons of the gelatinous substance of the spinal cord (SG). Thick and thin nerve fibers form a synaptic connection with the neurons of the posterior horns of the spinal cord (T), as well as with the neurons of the gelatinous substance (SG). At the same time, thick fibers increase, and thin fibers inhibit, reduce the activity of SG neurons. In turn, SG neurons play the role of gates that open or close the pathways for impulses that excite T-neurons of the spinal cord.

If the impulsation comes through thick fibers, then inhibitory SG neurons are activated, the "gates" are closed, and pain impulses through thin nerve fibers do not enter the dorsal horns of the spinal cord.

When thick myelin fibers are damaged, their inhibitory effect on SG neurons decreases and the "gates" open. In this case, pain impulses pass through thin nerve fibers to the T-neurons of the spinal cord and form a feeling of pain. From this point of view it is possible to explain the mechanisms of occurrence of phantom pains. During amputation of a limb, thick nerve fibers suffer to a greater extent, the processes of inhibition of SG neurons are disturbed, the "gates" open and pain impulses enter T-neurons through thin fibers.

Theory of generator and systemic mechanisms of pain

This is the theory of G.N. Kryzhanovsky. According to this theory, the formation of pathologically enhanced excitation generators (GPUV) in the nociceptive system plays a significant role in the occurrence of pathological pain. They occur if the pain stimulation is long enough and is able to overcome the "gate" control.

Such a GPUV is a complex of hyperreactive neurons capable of maintaining increased activity without additional stimulation from the periphery or from other sources. HPUV can occur not only in the system of afferent input to the spinal cord, but also in other parts of the nociceptive system. Under the influence of the primary HPSV, other systems of pain sensitivity are involved in the pathological process, which together form a pathological system with increased sensitivity. This pathological system is the pathophysiological basis of the pain syndrome.

Mechanisms of pain development

The main mechanisms of pain are:

1. Neurophysiological mechanisms

2. Neurochemical mechanisms

Neurophysiological mechanisms of pain formation are presented:

1. Receptor mechanism

2. Conductor mechanism

3. Central mechanism

Receptor mechanism

Both polymodal receptors and specific nociceptive receptors have the ability to perceive a painful stimulus. Polymodal receptors are represented by a group of mechanoreceptors, chemoreceptors, and thermoreceptors located both on the skin surface and in internal organs and the vascular wall. The impact on the receptors of a superstrong stimulus leads to the appearance of a pain impulse. An overstrain of auditory and visual analyzers plays an important role in the formation of pain. So, superstrong sound vibrations cause a pronounced pain sensation, up to a violation of the central nervous system function (airfields, train stations, discos). A similar reaction is caused by irritation of visual analyzers (light effects at concerts, discos).

The number of pain (nociceptive) receptors in different organs and tissues is not the same. Some of these receptors are located in the vascular wall, joints. Their greatest number is found in the dental pulp, the cornea of the eye, and the periosteum.

From pain and polymodal receptors, impulses are transmitted along peripheral nerves to the spinal cord and central nervous system.

Conductor mechanism

This mechanism is represented by thick and thin myelin and thin non-myelin fibers.

Primary, epicritical, pain is caused by the conduction of a pain signal along myelin fibers of type A  . Secondary, protopathic, pain is caused by the conduction of excitation along thin, slowly conducting fibers of type C. Violation of the trophism of the nerve leads to blockade of tactile sensitivity along thick pulpy nerves, but the sensation of pain persists. Under the action of local anesthetics, pain sensitivity first disappears, and then tactile sensitivity. This is due to the termination of the conduction of excitation along thin unmyelinated type C fibers. Thick myelinated fibers are more sensitive to a lack of oxygen than thin fibers. Damaged nerves are more sensitive to various humoral influences (histamine, bradykinin, potassium ions), to which they do not respond under normal conditions.

Central Pain Mechanisms

The central pathophysiological mechanisms of pathological pain are the formation and activity of generators of increased excitability in any part of the nociceptive system. For example, the reason for the appearance of such generators in the dorsal horns of the spinal cord may be enhanced long-term stimulation of peripheral damaged nerves. With chronic clamping of the infraorbital branch of the trigeminal nerve, pathologically enhanced electrical activity and the formation of a pathologically enhanced excitation generator appear in its caudal nucleus. Thus, pain of peripheral origin acquires the character of a central pain syndrome.

The reason for the emergence of generators of increased excitability may be partial deafferentation of neurons. During deafferentation, there is an increase in the excitability of nerve structures, a violation of inhibition and disinhibition of deafferent neurons, and a violation of their trophism. An increase in the sensitivity of tissues to pain impulses can also occur with denervation syndrome. In this case, there is an increase in the area of receptor zones that can respond to catecholamines and other biologically active substances and increase the feeling of pain.

The trigger mechanism for the development of pain is the primary generator of pathologically enhanced excitation. Under its influence, the functional state of other departments of pain sensitivity changes, the excitability of their neurons increases. Gradually, secondary generators are formed in different parts of the nociceptive system with involvement in the pathological process of the higher parts of pain sensitivity - the thalamus, somatosensory and orbitofrontal cortex of the brain. These zones carry out the perception of pain and determine its nature.

The central mechanisms of pain sensitivity are represented by the following formations. The neuron that responds to a nociceptive stimulus is located in the dorsal ganglion (D). As part of the posterior roots, the conductors of this ganglion enter the spinal cord and terminate on the neurons of the posterior horns of the spinal cord (T), forming synaptic contacts with them. The processes of T-neurons along the spinothalamic tract (3) transmit excitation to the visual tubercles (4) and terminate on the neurons of the ventrobasal complex of the thalamus (5). The neurons of the thalamus transmit impulses to the cerebral cortex, which determines the process of awareness of pain in a certain area of the body. The greatest role in this process belongs to the somatosensory and orbitofrontal zones. With the participation of these zones, responses to nociceptive stimuli from the periphery are realized.

Ganglion T-neuron Cortex

In addition to the cerebral cortex, a significant role in the formation of pain belongs to the thalamus, where nociceptive irritation takes on the character of an unpleasant painful feeling. If the cerebral cortex ceases to control the activity of the underlying sections, then thalamic pain is formed without a clear localization.

Localization and type of pain also depends on the inclusion in the process of other formations of the nervous system. An important structure that processes the pain signal is the reticular formation. When it is destroyed, the conduction of a pain impulse to the cerebral cortex is blocked and the adrenergic response of the reticular formation to pain stimulation is turned off.

The limbic system plays an important role in the development of pain. The participation of the limbic system is determined by the formation of pain impulses coming from the internal organs: this system is involved in the formation of visceral pain. Irritation of the cervical sympathetic node causes severe pain in the teeth, lower jaw, ear. When the fibers of the somatic innervation are clamped, somatolgia occurs, localized in the zone of innervation of the peripheral nerves and their roots.

In some cases, with prolonged irritation of damaged peripheral nerves (trigeminal, facial, sciatic), a pain syndrome may develop, which is characterized by intense burning pains and is accompanied by vascular and trophic disorders. This mechanism underlies causalgia.

Neurochemical mechanisms of pain

Functional neurophysiological mechanisms of the activity of the pain sensitivity system are implemented by neurochemical processes.

Peripheral pain receptors are activated under the influence of many endogenous biologically active substances: histamine, substance P, kinins, prostaglandins, leukotrienes, potassium and hydrogen ions. It has been shown that stimulation of pain receptors leads to the release of neuropeptides, such as substance P, by unmyelinated type C nerve fibers. This is a pain mediator. Under certain conditions, it can promote the release of biologically active substances: histamine, prostaglandins, leukotrienes. The latter increase the sensitivity of nociceptors to kinins.

Substance P Prostaglandins, Kinin Sensitization

leukotriene receptors

An important role in the formation of pain is played by potassium and hydrogen ions. They facilitate the depolarization of receptors and contribute to the emergence of an afferent pain signal in them. With increased nociceptive stimulation, a significant amount of excitatory substances, in particular, glutamate, appears in the posterior horns of the spinal cord. These substances cause the depolarization of neurons and are one of the mechanisms for the formation of generators of pathologically enhanced excitation.

Antinociceptive system

Humoral Opiates Serotonin

mechanisms

Norepinephrine

ANTINOCI-

CEPTIVE

Inhibition of ascending pain

Neurogenic sensitivities in neurons

mechanisms of gray matter, subcortical

structures and nuclei of the cerebellum

The formation of a pain impulse is closely related to the functional state of the antinociceptive system. The antinociceptive system realizes its influence through neurogenic and humoral mechanisms. Activation of neurogenic mechanisms leads to blockade of ascending pain impulses. When neurogenic mechanisms are disturbed, painful stimuli of even low intensity cause severe pain. This may occur in case of insufficiency of antinociceptive mechanisms responsible for the "gateway" control system, for example, in CNS injuries, neuroinfections.

Neurochemical mechanisms play an important role in the activity of the antinociceptive system. They are realized by endogenous peptides and mediators.

Opioid neuropeptides (enkephalins, -endorphins) are effective endogenous analgesics. They inhibit nociceptive neurons, change the activity of neurons in the higher parts of the brain that perceive pain impulses and participate in the formation of pain sensation. Their effects are realized through the action of serotonin, norepinephrine and gamma-aminobutyric acid.

OPIATES SEROTONIN

NORADRENALINE

Serotonin is a mediator of the antinociceptive system at the spinal level. With an increase in the content of serotonin in the central nervous system, pain sensitivity decreases, and the effect of morphine increases. A decrease in the concentration of serotonin in the central nervous system increases pain sensitivity.

Norepinephrine inhibits the activity of nociceptive neurons of the dorsal horns of the spinal cord and nuclei of the trigeminal nerve. Its analgesic effect is associated with the activation of -adrenergic receptors, as well as with the involvement of the serotonergic system in the process.

Gamma-aminobutyric acid (GABA) is involved in the suppression of the activity of nociceptive neurons to pain at the spinal level, in the region of the posterior horns. Violation of inhibitory processes associated with a decrease in GABA activity causes the formation of generators of pathologically enhanced excitation in the posterior horns of the spinal cord. This leads to the development of severe pain syndrome of spinal origin.

Violation of autonomic functions in pain

With severe pain in the blood, the level of corticosteroids, catecholamines, growth hormone, glucagon, -endorphin increases and the content of insulin and testosterone decreases. From the side of the cardiovascular system, hypertension, tachycardia are observed due to the activation of the sympathetic nervous system. With pain, changes in breathing manifest themselves in the form of tachypnea, hypocapnia. The acid-base state is disturbed. With severe pain, breathing becomes irregular. Restricted pulmonary ventilation.

With pain, hypercoagulation processes are activated. Hypercoagulation is based on an increase in thrombin formation and an increase in plasma thromboplastin activity. With excessive production of adrenaline from the vascular wall, tissue thromboplastin enters the bloodstream. Hypercoagulation is especially pronounced in myocardial infarction, accompanied by pain.

With the development of pain, lipid peroxidation is activated and the production of proteolytic enzymes increases, which causes tissue destruction. Pain contributes to the development of tissue hypoxia, impaired microcirculation and dystrophic processes in tissues.

Pain – algos, or nociception, is an unpleasant sensation realized by a special system of pain sensitivity and higher parts of the brain related to the regulation of the psycho-emotional sphere. In practice, pain always signals the impact of such exogenous and endogenous factors that cause tissue damage, or the consequences of damaging effects. Pain impulses form the response of the body, which is aimed at avoiding or eliminating the pain that has arisen. In this case physiological adaptive role of pain, which protects the body from excessive nociceptive effects, is transformed into a pathological one. In pathology, pain loses the physiological quality of adaptation and acquires new properties - disadaptation, which is its pathogenic significance for the body.

pathological pain is carried out by an altered system of pain sensitivity and leads to the development of structural and functional shifts and damage in the cardiovascular system, internal organs, microcirculatory bed, causes tissue dystrophy, impaired autonomic reactions, changes in the activity of the nervous, endocrine, immune and other body systems. Pathological pain depresses the psyche, causes excruciating suffering to the patient, sometimes obscuring the underlying disease and leading to disability.

Since the time of Sherrington (1906) it has been known that pain receptors are nociceptors are bare axial cylinders. Their total number reaches 2-4 million, and on average there are about 100-200 nociceptors per 1 cm2. Their excitation is directed to the central nervous system through two groups of nerve fibers - mainly thin myelinated (1-4 microns) groups BUT[the so-called BUT-δ ( BUT-delta) with an average excitation velocity of 18 m/s] and thin unmyelized (1 µm or less) groups FROM(conduction speed 0.4-1.3 m/s). There are indications of participation in this process of thicker (8-12 microns) myelinated fibers with a speed of excitation of 40-70 m/s - the so-called BUT-β fibers. It is quite possible that it is precisely due to differences in the speed of propagation of excitation impulses that an initially acute, but short-term pain sensation (epicritic pain) is consistently perceived, and then, after some time, dull, aching pain (protopathic pain).

Nociceptive endings of the afferent fibers of the group BUT-δ ( mechanociceptors, thermonociceptors, chemociceptors ) are activated by strong mechanical and thermal stimuli inadequate for them, while the endings of the afferent fibers of the group FROM are excited by both chemical agents (mediators of inflammation, allergies, acute phase response, etc.), and mechanical and thermal stimuli, in connection with which they are usually called polymodal nociceptors. Chemical agents that activate nociceptors are most often biologically active substances (histamine, sertonin, kinins, prostaglandins, cytokines) and they are called algesic agents, or algogens.

Nerve fibers that conduct pain sensitivity and are axons of pseudounipolar neurons of the paraspinal ganglia enter the spinal cord as part of the posterior roots and form synaptic contacts with specific nociceptive neurons of its posterior horns within I-II, as well as in V and VII plates. Relay neurons of the 1st plate of the spinal cord (the first group of nerve cells) that respond exclusively to pain stimuli are called specific nociceptive neurons, and the nerve cells of the second group that respond to nociceptive mechanical, chemical and thermal stimuli are called "wide dynamic range" neurons, or neurons with multiple receptive fields. They are localized in the V-VII plates. The third group of nociceptive neurons is located in the gelatinous substance of the second lamina of the dorsal horn and influences the formation of the ascending nociceptive flow, directly affecting the activity of the cells of the first two groups (the so-called "gate pain control").

Crossing and non-crossing axons of these neurons form the spinothalamic tract, which occupies the anterolateral sections of the white matter of the spinal cord. In the spinothalamic tract, neospinal (located laterally) and paleospinal (located medially) portions are isolated. The neospinal part of the spinothalamic tract ends in the ventrobasal nuclei, while the paleospinal part ends in the intralaminar nuclei of the thalamus opticus. Previously, the paleospinal system of the spinothalamic tract contacts the neurons of the reticular formation of the brainstem. In the nuclei of the thalamus there is a third neuron, the axon of which reaches the somatosensory zone of the cerebral cortex (S I and S II). The axons of the intralaminar nuclei of the thalamus of the paleospinal part of the spinothalamic tract project onto the limbic and frontal cortex.

Therefore, pathological pain (more than 250 shades of pain are known) occurs when both peripheral nerve structures (nociceptors, nociceptive fibers of peripheral nerves - roots, cords, spinal ganglia) are damaged or irritated, and central (gelatinous substance, ascending spinothalamic pathways, synapses on different levels of the spinal cord, the medial loop of the trunk, including the thalamus, the internal capsule, the cerebral cortex). Pathological pain occurs due to the formation of a pathological algic system in the nociceptive system.

Peripheral sources of pathological pain. They can be tissue receptors with their enhanced and prolonged irritation (for example, due to inflammation), the action of tissue decay products (tumor growth), chronically damaged and regenerating sensory nerves (compression with a scar, callus, etc.), demyelinated regenerating fibers of damaged nerves, etc.

Damaged and regenerating nerves are very sensitive to the action of humoral factors (K + , adrenaline, serotonin and many other substances), while under normal conditions they do not have such increased sensitivity. Thus, they become a source of continuous stimulation of nociceptors, as, for example, it takes place during the formation of a neuroma - a formation of chaotically overgrown and intertwined afferent fibers, which occurs during their disordered regeneration. It is the elements of the neuroma that show extremely high sensitivity to mechanical, physical, chemical and biological factors of influence, causing causalgia- paroxysmal pain, provoked by a variety of influences, including emotional ones. Here we note that the pain that occurs in connection with damage to the nerves is called neuropathic.

Central sources of pathological pain. Prolonged and sufficiently intense nociceptive stimulation can cause the formation of a pathologically enhanced excitation generator (GPUV), which can form at any level of the CNS within the nociceptive system. HPUV morphologically and functionally is an aggregate of hyperactive neurons that reproduces an intense uncontrolled stream of impulses or an output signal. The formation and subsequent functioning of the GPUV is a typical pathological process in the CNS, which is realized at the level of interneuronal relationships.

Incentive mechanisms for the formation of the GPU can be:

1. Sustained, pronounced and prolonged depolarization of the neuron membrane;

2. Violations of inhibitory mechanisms in neural networks;

3. Partial deafferentation of neurons;

4. Trophic disorders of neurons;

5. Damage to neurons and changes in their environment.

Under natural conditions, the occurrence of HPSV occurs under the influence of (1) prolonged and enhanced synaptic stimulation of neurons, (2) chronic hypoxia, (3) ischemia, (4) microcirculation disorders, (5) chronic traumatization of nerve structures, (6) the action of neurotoxic poisons, (7) violation of the propagation of impulses along the afferent nerves.

In an experiment, HPUV can be reproduced by exposing certain parts of the CNS to various convulsants or other stimulants (application of penicillin, glutamate, tetanus toxin, potassium ions, etc.) to the brain.

An obligatory condition for the formation and activity of GPUV is the insufficiency of inhibitory mechanisms in the population of interested neurons. An increase in the excitability of a neuron and activating synaptic and non-synaptic interneuronal connections are of great importance. As the disturbance increases, the population of neurons transforms from a transfer relay, which it performed normally, into a generator that generates an intense and prolonged stream of impulses. Once having arisen, excitation in the generator can be maintained for an indefinitely long time, no longer needing additional stimulation from other sources. Additional stimulation may play a triggering role or activate the GPUV or promote its activity. An example of self-sustaining and self-developing activity can be GPV in the trigeminal nuclei (trigeminal neuralgia), pain syndrome of spinal origin in the posterior horns of the spinal cord, and thalamic pain in the thalamic region. The conditions and mechanisms for the formation of HPSV in the nociceptive system are fundamentally the same as in other parts of the CNS.

The reasons for the occurrence of HPUV in the posterior horns of the spinal cord and the nuclei of the trigeminal nerve may be increased and prolonged stimulation from the periphery, for example, from damaged nerves. Under these conditions, pain of initially peripheral origin acquires the properties of a central generator, and may have the character of a central pain syndrome. An obligatory condition for the emergence and functioning of the painful GPUV in any link of the nociceptive system is insufficient inhibition of the neurons of this system.

The causes of HPUV in the nociceptive system may be partial deafferentation of neurons, for example, after a break or damage to the sciatic nerve or dorsal roots. Under these conditions, epileptiform activity is recorded electrophysiologically, initially in the deafferented posterior horn (a sign of HPUV formation), and then in the nuclei of the thalamus and sensorimotor cortex. The deafferentation pain syndrome that occurs under these conditions has the character of a phantom pain syndrome - pain in a limb or other organ that is absent as a result of amputation. In such people, pain is projected onto certain areas of a non-existent or numb limb. HPUV and, accordingly, pain syndrome can occur in the posterior horns of the spinal cord and thalamic nuclei when they are locally exposed to certain pharmacological preparations - convulsants and biologically active substances (for example, tetanus toxin, potassium ions, etc.). Against the background of the activity of the GPU, the application of inhibitory mediators - glycine, GABA, etc. on the area of the central nervous system where it functions, it stops the pain syndrome for the duration of the mediator action. A similar effect is observed when using calcium channel blockers - verapamil, nifedipine, magnesium ions, as well as anticonvulsants, for example, carbamazepam.

Under the influence of a functioning GPUV, the functional state of other parts of the pain sensitivity system changes, the excitability of their neurons increases, and there is a tendency for the emergence of a population of nerve cells with prolonged increased pathological activity. Over time, secondary HPUV can form in different parts of the nociceptive system. Perhaps the most significant for the body is the involvement in the pathological process of the higher parts of this system - the thalamus, somatosensory and fronto-orbital cortex, which carry out the perception of pain and determine its nature. The structures of the emotional sphere and the autonomic nervous system are also involved in the pathology of the algic system.

antinociceptive system. The system of pain sensitivity - nociception includes its functional antipode - the antinociceptive system, which acts as a regulator of the activity of nociception. Structurally, the antinociceptive, like the nociceptive system, is represented by the same nerve formations of the spinal cord and brain, where the relay functions of nociception are carried out. The implementation of the activity of the antinociceptive system is carried out through specialized neurophysiological and neurochemical mechanisms.

The antinociceptive system ensures the prevention and elimination of the pathological pain that has arisen - the pathological algic system. It turns on with excessive pain signals, weakening the flow of nociceptive impulses from its sources, and thereby reduces the intensity of pain sensation. Thus, the pain remains under control and does not acquire its pathological significance. It becomes clear that if the activity of the antinociceptive system is grossly impaired, then even pain stimuli of minimal intensity cause excessive pain. This is observed in some forms of congenital and acquired insufficiency of the antinociceptive system. In addition, there may be a discrepancy in the intensity and quality of the formation of epicritical and protopathic pain sensitivity.

In case of insufficiency of the antinociceptive system, which is accompanied by the formation of pain that is excessive in intensity, additional stimulation of antinociception is necessary. Activation of the antinociceptive system can be carried out by direct electrical stimulation of certain brain structures, for example, raphe nuclei through chronically implanted electrodes, where there is a neuronal antinociceptive substrate. This was the basis for considering this and other brain structures as the main centers of pain modulation. The most important center of pain modulation is the region of the midbrain, located in the region of the Sylvian aqueduct. Activation of the periaqueductal gray matter causes prolonged and deep analgesia. The inhibitory effect of these structures is carried out through descending pathways from the large raphe nucleus and the blue spot, where there are serotonergic and noradrenergic neurons that send their axons to the nociceptive structures of the spinal cord, which carry out their presynaptic and postsynaptic inhibition.

Opioid analgesics have a stimulating effect on the antinociceptive system, although they can also act on nociceptive structures. Significantly activate the functions of the antinociceptive system and some physiotherapeutic procedures, especially acupuncture (acupuncture).

The opposite situation is also possible, when the activity of the antinociceptive system remains extremely high, and then there may be a threat of a sharp decrease and even suppression of pain sensitivity. Such a pathology occurs during the formation of HPUV in the structures of the antinociceptive system itself. As examples of this kind, one can point to the loss of pain sensitivity during hysteria, psychosis, and stress.

Neurochemical mechanisms of pain. Neurophysiological mechanisms of the activity of the pain sensitivity system are implemented by neurochemical processes at various levels of the nociceptive and antinociceptive systems.

Peripheral nociceptors are activated by many endogenous biologically active substances: histamine, bradykinin, prostaglandins, and others. However, substance P, which is considered in the nociception system as a pain mediator, is of particular importance in conducting excitation in primary nociceptive neurons. With enhanced nociceptive stimulation, especially from peripheral sources in the dorsal horn of the spinal cord, many mediators can be detected, including pain mediators, among which are excitatory amino acids (glycine, aspartic, glutamic and other acids). Some of them do not belong to pain mediators, however, they depolarize the neuron membrane, creating the preconditions for the formation of GPUV (for example, glutamate).

Deafferentation and/or denervation of the sciatic nerve leads to a decrease in the content of substance P in the neurons of the dorsal horns of the spinal cord. On the other hand, the content of another pain mediator, VIP (vasointestinal inhibitory polypeptide), sharply increases, which under these conditions, as it were, replaces the effects of substance P.

The neurochemical mechanisms of the activity of the antinociceptive system are implemented by endogenous neuropeptides and classical neurotransmitters. Analgesia is caused, as a rule, by a combination or sequential action of several transmitters. The most effective endogenous analgesics are opioid neuropeptides - enkephalins, beta-endorphins, dynorphins, which act through specific receptors on the same cells as morphine. On the one hand, their action inhibits the activity of transmission nociceptive neurons and changes the activity of neurons in the central links of pain perception, on the other hand, it increases the excitability of antinociceptive neurons. Opiate receptors are synthesized within the bodies of nociceptive central and peripheral neurons and are then expressed via axoplasmic transport on the surface of membranes, including those of peripheral nociceptors.

Endogenous opioid peptides have been found in various structures of the CNS involved in the transmission or modulation of nociceptive information - in the gelatinous substance of the posterior horns of the spinal cord, in the medulla oblongata, in the gray matter of the periaqueductal structures of the midbrain, the hypothalamus, as well as in the neuroendocrine glands - the pituitary and adrenal glands. On the periphery, the most likely source of endogenous ligands for opiate receptors can be cells of the immune system - macrophages, monocytes, T- and B-lymphocytes, which synthesize under the influence of interleukin-1 (and, possibly, with the participation of other cytokines) all three known endogenous neuropeptides - endorphin, enkephalin and dynorphin.

Realization of effects in the antinociceptive system occurs not only under the influence of substance P, but also with the participation of other neurotransmitters - serotonin, norepinephrine, dopamine, GABA. Serotonin is a mediator of the antinociceptive system at the level of the spinal cord. Norepinephrine, in addition to participating in the mechanisms of antinociception at the spinal level, has an inhibitory effect on the formation of pain sensations in the brainstem, namely, in the nuclei of the trigeminal nerve. It should be noted the role of norepinephrine as a mediator of antinociception in the excitation of alpha-adrenergic receptors, as well as its participation in the serotonergic system. GABA is involved in the suppression of the activity of nociceptive neurons for pain at the spinal level. Violation of GABAergic inhibitory processes causes the formation of HPS in spinal neurons and a severe pain syndrome of spinal origin. At the same time, GABA can inhibit the activity of neurons in the antinociceptive system of the medulla oblongata and midbrain, and thus weaken the mechanisms of pain relief. Endogenous enkephalins can prevent GABAergic inhibition and thus enhance downstream antinociceptive effects.

The mechanisms of regulation of pain sensitivity are diverse and include both nervous and humoral components. The patterns that regulate the relationship of nerve centers are completely valid for everything that is associated with pain. This includes the phenomena of inhibition or, conversely, increased excitation in various structures of the nervous system associated with pain, when a sufficiently intense impulse from other neurons occurs.

But humoral factors play a particularly important role in the regulation of pain sensitivity.

Firstly, the algogenic substances already mentioned above (histamine, bradykinin, serotonin, etc.), sharply increasing nociceptive impulses, form an appropriate reaction in the central nervous structures.

Secondly, the so-called substance pi. It is found in large quantities in the neurons of the dorsal horns of the spinal cord and has a pronounced algogenic effect, facilitating the responses of nociceptive neurons, causing excitation of all high-threshold neurons of the dorsal horns of the spinal cord, that is, it plays a neurotransmitter (transmitting) role during nociceptive impulses at the level of the spinal cord. Axodendritic, axosomatic and axo-axonal synapses have been found, the terminals of which contain substance π in the vesicles.

Thirdly, nociception is suppressed by such an inhibitory mediator of the central nervous system as γ-aminobutyric acid.

And, finally, fourthly, an extremely important role in the regulation of nociception is played by endogenous opioid system.

In experiments using radioactive morphine, specific sites of its binding in the body were found. The discovered areas of morphine fixation are called opiate receptors. The study of the areas of their localization showed that the highest density of these receptors was noted in the region of the terminals of the primary afferent structures, the gelatinous substance of the spinal cord, the giant cell nucleus and the nuclei of the thalamus, the hypothalamus, the central gray periaqueductal substance, the reticular formation, and the raphe nuclei. Opiate receptors are widely represented not only in the central nervous system, but also in its peripheral parts, in the internal organs. It has been suggested that the analgesic effect of morphine is determined by the fact that it binds the accumulation sites of opioid receptors and helps to reduce the release of algogenic mediators, which leads to the blockade of nociceptive impulses. The existence of an extensive network of specialized opioid receptors in the body has determined the purposeful search for endogenous morphine-like substances.

In 1975, oligopeptides, that bind opioid receptors. These substances are called endorphins and enkephalins. In 1976 β-endorphin was isolated from human cerebrospinal fluid. Currently, α-, β- and γ-endorphins, as well as methionine- and leucine-enkephalins are known. The hypothalamus and pituitary gland are considered the main areas for the production of endorphins. Most endogenous opioids have a powerful analgesic effect, but different parts of the CNS have unequal sensitivity to their fractions. It is believed that enkephalins are also mainly produced in the hypothalamus. Endorphin terminals are more limited in the brain than enkephalin ones. The presence of at least five types of endogenous opioids also implies the heterogeneity of opioid receptors, which so far have been isolated only by five types, which are unequally represented in nerve formations.

Assume two mechanisms of action of endogenous opioids:

1. Through the activation of hypothalamic and then pituitary endorphins and their systemic action due to distribution with blood flow and cerebrospinal fluid;

2. Through the activation of terminals. containing both types of opioids, with subsequent action directly on the opiate receptors of various structures of the central nervous system and peripheral nerve formations.

Morphine and most endogenous opiates block the conduction of nociceptive impulses already at the level of both somatic and visceral receptors. In particular, these substances reduce the level of bradykinin in the lesion and block the algogenic effect of prostaglandins. At the level of the posterior roots of the spinal cord, opioids cause depolarization of the primary afferent structures, enhancing presynaptic inhibition in the somatic and visceral afferent systems.

Chapter 2 PATHOPHYSIOLOGY OF PAIN

Pain as a sensation

The sensation of pain is a function of the cerebral hemispheres. However, in life, along with irritation of pain receptors, other receptors are also excited. Therefore, pain occurs in combination with other sensations.

1. Feelings can influence each other. The feeling of pain can be relieved by another strong irritation: food, sexual, etc. (I.P. Pavlov).

2. The sensation of pain is largely determined by the initial state of the cerebral cortex. The pain is more excruciating when waiting for it. On the contrary, when the cortex is depressed, the pain weakens and even disappears. Persons in a state of passion (sharp excitement) do not feel pain (fighters at the front).

Leriche R., considering the evolution of pain over the past 100 years, notes a decrease in resistance to pain (analgesics, pain relief, other education of the nervous system). Irasek said: “Modern man does not want to suffer from pain, is afraid of it and does not intend to endure it”. According to Ged, the feeling of pain is diffuse and localized only due to the simultaneous stimulation of tactile formations. The internal organs, obviously, receive only fibers of non-localized gross pain sensitivity. This explains the inability of patients to accurately localize the pain focus. This also explains the presence of reflected pain (Ged's zone).

Ways of perception and conduction of pain sensations

Most domestic and foreign scientists adhere to the point of view that allows the existence of specialized nerve devices that perceive pain and associated pathways. The second point of view is that specific types of irritation (temperature, tactile, etc.), outgrowing certain threshold values, become destructive and are perceived as painful (objection - with local anesthesia, the feeling of pain is eliminated, but the feeling of touch and pressure is preserved). Luciani's observation is direct evidence of the presence of separate paths of pain sensitivity. One Swiss doctor had an exceptional ability to assess the state of the pulse and internal organs with the help of palpation, i.e. tactile sensitivity was well developed. However, this doctor was completely unaware of the feeling of pain. When examining his spinal cord, it turned out that groups of small cells in the posterior horns of the gray matter were completely atrophied, which was the reason for the lack of pain sensitivity.

The perception of pain is associated with the presence of free nerve endings in various morphological structures of the body. Especially a lot of them in the skin (up to 200 per 1 cm 2). Free nerve endings were not found in the substance of the brain, visceral pleura and lung parenchyma.

Any impact leading to denaturation of the cytoplasm causes a burst of impulses in free nerve endings. In this case, tissue respiration is disturbed, and H-substances (apetylcholine, histamine, etc.) are released. These substances are found in biological fluids and, apparently, contribute to the appearance of pain (mosquito venom, nettle). Conduction of pain is carried out by fibers of two groups: thin myelin (B) and thin non-myelin (C). Since the speed of impulse conduction in these fibers is different, with a short irritation, the pain sensation manifests itself in two stages. Initially, a finely localized feeling of brief pain occurs, followed by an “echo” in the form of a flash of diffuse pain of considerable intensity. The interval between these phases of perception is the greater, the farther the place of stimulation is from the brain.

The further path of pain irritation passes through the posterior roots to the dorsolateral tract of Lissauer. Rising upward, the pain pathways reach the visual halls and end on the cells of the posterior ventral nuclei. In recent years, evidence has been obtained in favor of the fact that part of the pain-transmitting fibers is lost in the reticular formation and the hypothalamus.

Let me remind you that the reticular formation extends from the upper segments of the spinal cord to the visual tubercles, sub- and hypothalamic regions. The most important anatomical and physiological feature of the reticular formation is that it collects all afferent stimuli. Due to this, it has a high energy potential and has an upward activating effect on the cerebral cortex. In turn, the cerebral cortex has a downward inhibitory effect on the reticular formation. This dynamic cortical-subcortical balance maintains the waking state of a person. The cortex is in close relationship with the nuclei of most cranial nerves, the respiratory, vasomotor and vomiting centers, the spinal cord, the thalamus and the hypothalamus.

Thus, pain impulses enter the cerebral cortex in two ways: through the reticular formation system and along the classical sensory tract. The relation of the diffuse thalamic projection to the so-called associative fields of the cloak (frontal lobes) is especially close. This suggests that this area receives the greatest number of painful stimuli. Part of the pain conductors enters the region of the posterior central gyrus.

So, the ways of conducting pain in the periphery are more or less known. With regard to intracentral transmission, further verification and clarification is needed. However, the fact that the largest number of impulses enters the frontal lobes can be considered proven.

Nerve centers that receive impulses from the periphery function according to the type of dominant A. L. Ukhtomsky. The dominant focus not only extinguishes the effects of other stimuli, but the excitation in it is enhanced by them and can take on a stable character. If the center that transmits pain impulses becomes such a focus, then the pain acquires a special intensity and stability (read below).

The body's response to pain

The flow of pain impulses causes a number of characteristic shifts in the body. Mental activity focuses on the organization of measures to protect against pain. This causes skeletal muscle tension and a powerful vocal and defensive response.

Changes in the cardiovascular system: tachycardia occurs, blood pressure decreases, there may be bradycardia and cardiac arrest with very severe pain, spasm of peripheral vessels, centralization of blood circulation with a decrease in BCC. Painful irritation often causes depression and respiratory arrest, followed by rapid and arrhythmic breathing, oxygen supply is disrupted (due to hypocapnia, the dissociation of oxyhemoglobin is disrupted) - oxygen is poorly given to tissues.

Changes in the function of the gastrointestinal tract and urination: most often there is a complete inhibition of the secretion of the digestive glands, diarrhea, involuntary urination, anuria, the latter is often replaced by polyuria. All types of metabolism change. Metabolic acidosis occurs. Violated water, electrolyte, energy metabolism.

Hormonal shifts: the bloodstream is flooded with adrenaline, norepinephrine, hydrocortisone. According to Selye, in response to an extreme impact (pain), a state of general systemic tension is created in the body - “stress”. It has three phases:

1. Emergency (anxiety), occurs immediately after exposure to the agent (symptoms of excitation of the sympathetic-adrenal system come to the fore).

2. Phase of resistance (adaptation) - adaptation is optimal.

3. Phase of exhaustion, when adaptation is lost - inhibition of all functions and death.

It is hard to imagine that the organism, with its expedient arrangement, left the cerebral cortex defenseless. The patient in severe shock soberly assesses the situation. Apparently, pain trauma creates a center of inhibition somewhere lower. It has been experimentally proven (irritation of the sciatic nerve) that inhibition develops in the reticular formation, while the cortex retains its functional ability. It would be good (to protect the patient from pain) to deepen inhibition in the reticular formation, if it were not so intimately connected with the respiratory and vasomotor centers.

Every person in his life has experienced pain - an unpleasant sensation with negative emotional experiences. Often pain performs a signaling function, warns the body of danger and protects it from possible excessive damage. Such pain called physiological.

Perception, conduction and analysis of pain signals in the body are provided by special neuronal structures of the nociceptive system, which are part of the somatosensory analyzer. Therefore, pain can be considered as one of the sensory modalities necessary for normal life and warning us of danger.

However, there is also pathological pain. This pain makes people unable to work, reduces their activity, causes psycho-emotional disorders, leads to regional and systemic microcirculation disorders, is the cause of secondary immune depression and disruption of the visceral systems. In a biological sense, pathological pain is a danger to the body, causing a whole range of maladaptive reactions.

Pain is always subjective. The final assessment of pain is determined by the location and nature of the damage, the nature of the damaging factor, the psychological state of the person and his individual experience.

There are five main components in the overall structure of pain:

Perceptual - allows you to determine the location of damage.
Emotional-affective - reflects the psycho-emotional reaction to damage.
Vegetative - associated with a reflex change in the tone of the sympathoadrenal system.
Motor - aimed at eliminating the action of damaging stimuli.
Cognitive - participates in the formation of a subjective attitude to the pain currently experienced on the basis of accumulated experience.

According to time parameters, acute and chronic pain are distinguished.

acute pain- new, recent pain, inextricably linked to the injury that caused it. As a rule, it is a symptom of any disease, injury, surgical intervention.

chronic pain- often acquires the status of an independent disease. It goes on for a long period of time. The cause of this pain in some cases may not be determined.

Nociception includes 4 main physiological processes:

1. transduction - the damaging effect is transformed in the form of electrical activity at the endings of sensory nerves.

2. Transmission - conduction of impulses along the system of sensory nerves through the spinal cord to the thalamocortical zone.

3. Modulation - modification of nociceptive impulses in the structures of the spinal cord.

4. Perception - the final process of perception of the transmitted impulses by a specific person with his individual characteristics, and the formation of a sensation of pain (Fig. 1).

Rice. 1. Basic physiological processes of nociception

Depending on the pathogenesis, pain syndromes are divided into:

Somatogenic (nociceptive pain).
Neurogenic (neuropathic pain).
Psychogenic.

Somatogenic pain syndromes arise as a result of stimulation of superficial or deep tissue receptors (nociceptors): in trauma, inflammation, ischemia, tissue stretching. Clinically, among these syndromes, there are: post-traumatic, postoperative, myofascial, pain with joint inflammation, pain in cancer patients, pain with damage to internal organs, and many others.

Neurogenic pain syndromes occur when nerve fibers are damaged at any point from the primary afferent conduction system to the cortical structures of the central nervous system. This may be the result of dysfunction of the nerve cell itself or of the axon due to compression, inflammation, trauma, metabolic disorders, or degenerative changes.

Example: postherpetic, intercostal neuralgia, diabetic neuropathy, rupture of the nerve plexus, phantom pain syndrome.

Psychogenic- in their development, the leading role is given to psychological factors that initiate pain in the absence of any serious somatic disorders. Often pains of a psychological nature arise as a result of overstrain of any muscles, which is provoked by emotional conflicts or psychosocial problems. Psychogenic pain may be part of a hysterical reaction or occur as a delusion or hallucination in schizophrenia and disappear with adequate treatment of the underlying disease. Psychogenic include pain associated with depression, which does not precede it and does not have any other cause.

According to the definition of the International Association for the Study of Pain (IASP - Internatinal Association of the Stady of Pain):
"Pain is an unpleasant sensation and emotional experience associated with or described in terms of actual or potential tissue damage."

This definition indicates that the sensation of pain can occur not only in tissue damage or in conditions of tissue damage risk, but even in the absence of any damage. In other words, a person's interpretation of pain, their emotional response and behavior may not correlate with the severity of the injury.

Pathophysiological mechanisms of somatogenic pain syndromes

Clinically, somatogenic pain syndromes are manifested by the presence of constant pain and / or increased pain sensitivity in the area of damage or inflammation. Patients easily localize such pains, clearly define their intensity and nature. Over time, the zone of increased pain sensitivity can expand and go beyond the damaged tissues. Areas with increased pain sensitivity to damaging stimuli are called zones of hyperalgesia.

There are primary and secondary hyperalgesia:

Primary hyperalgesia covers damaged tissue. It is characterized by a decrease in pain threshold (BP) and pain tolerance to mechanical and thermal stimuli.

Secondary hyperalgesia localized outside the damage zone. Has a normal BP and reduced pain tolerance only to mechanical stimuli.

Mechanisms of primary hyperalgesia

In the area of damage, inflammatory mediators are released, including bradykinin, metabolites of arachidonic acid (prostaglandins and leukotrienes), biogenic amines, purines, and a number of other substances that interact with the corresponding receptors of nociceptive afferents (nociceptors) and increase the sensitivity (cause sensitization) of the latter to mechanical and damaging incentives (Fig. 2).

Currently, bradykinin, which has a direct and indirect effect on sensitive nerve endings, is of great importance in the manifestation of hyperalgesia. The direct action of bradykinin is mediated through Beta 2 receptors and is associated with the activation of membrane phospholipase C. Indirect action: bradykinin acts on various tissue elements - endothelial cells, fibroblasts, mast cells, macrophages and neutrophils, stimulates the formation of inflammatory mediators in them (for example, prostaglandins) , which, interacting with receptors on nerve endings, activate membrane adenylate cyclase. Adenylate cyclase and phospholipase-C stimulate the formation of enzymes that phosphorylate ion channel proteins. As a result, the permeability of the membrane for ions changes - the excitability of nerve endings and the ability to generate nerve impulses are disturbed.

Sensitization of nociceptors during tissue damage is facilitated not only by tissue and plasma algogens, but also by neuropeptides released from C-afferents: substance P, neurokinin-A, or calcitonin-gene-related peptide. These neuropeptides cause vasodilation, increase their permeability, promote the release of prostaglandin E 2, cytokinins and biogenic amines from mast cells and leukocytes.

The afferents of the sympathetic nervous system also influence the sensitization of nociceptors and the development of primary hyperalgesia. Increasing their sensitivity is mediated in two ways:

1. By increasing vascular permeability in the area of damage and increasing the concentration of inflammatory mediators (indirect route);

2. Due to the direct effect of norepinephrine and adrenaline (neurotransmitters of the sympathetic nervous system) on alpha 2-adrenergic receptors located on the nociceptor membrane.

Mechanisms of development of secondary hyperalgesia

Clinically, the area of secondary hyperalgesia is characterized by an increase in pain sensitivity to intense mechanical stimuli outside the injury zone and can be located at a sufficient distance from the injury site, including on the opposite side of the body. This phenomenon can be explained by the mechanisms of central neuroplasticity leading to persistent hyperexcitability of nociceptive neurons. This is confirmed by clinical and experimental data indicating that the zone of secondary hyperalgesia is preserved with the introduction of local anesthetics into the area of damage and is eliminated in the case of a blockade of neurons of the dorsal horn of the spinal cord.

Sensitization of neurons in the posterior horns of the spinal cord can be caused by various types of damage: thermal, mechanical, due to hypoxia, acute inflammation, electrical stimulation of C-afferents. Great importance in the sensitization of nociceptive neurons of the posterior horns is given to excitatory amino acids and neuropeptides that are released from presynaptic terminals under the action of nociceptive impulses: neurotransmitters - glutamate, aspartate; neuropeptides - substance P, neurokinin A, calcitonin-gene-related peptide and many others. Recently, nitric oxide (NO), which plays the role of an atypical extrasynaptic mediator in the brain, has been given great importance in the mechanisms of sensitization.

The sensitization of nociceptive neurons that has arisen as a result of tissue damage does not need additional feeding with impulses from the site of damage and can persist for several hours or days even after the cessation of the receipt of nociceptive impulses from the periphery.

Tissue damage also causes an increase in the excitability and reactivity of nociceptive neurons in the overlying centers, including the nuclei of the thalamus and the somatosensory cortex of the cerebral hemispheres. Thus, peripheral tissue damage triggers a cascade of pathophysiological and regulatory processes affecting the entire nociceptive system from tissue receptors to cortical neurons.

The most important links in the pathogenesis of somatogenic pain syndromes:

Irritation of nosoceptors in case of tissue damage.
Isolation of algogens and sensitization of nociceptors in the area of damage.
Increased nociceptive afferent flow from the periphery.
FROM ensitization of nociceptive neurons at various levels of the CNS.

In this regard, the use of agents aimed at:

suppression of the synthesis of inflammatory mediators- the use of nonsteroidal and / or steroidal anti-inflammatory drugs (suppression of the synthesis of algogens, a decrease in inflammatory reactions, a decrease in the sensitization of nociceptors);
limiting the flow of nociceptive impulses from the damaged area to the central nervous system- various blockades with local anesthetics (prevent sensitization of nociceptive neurons, contribute to the normalization of microcirculation in the area of damage);
activation of structures of the antinociceptive system- for this, depending on the clinical indications, a whole range of drugs can be used that reduce pain sensitivity and negative emotional experience:

1) medications - narcotic and non-narcotic analgesics, benzodiazepines, alpha 2-adrenergic agonists (clophelin, guanfacine) and others;

2) non-drug means - transcutaneous electrical nerve stimulation, reflexology, physiotherapy.

Rice. 2. Scheme of nerve pathways and some neurotransmitters involved in nociception

Pathophysiological mechanisms of neurogenic pain syndromes

Neurogenic pain syndromes occur when structures associated with the conduction of nociceptive signals are damaged, regardless of the location of damage to the pain pathways. This is supported by clinical observations. In patients after damage to the peripheral nerves in the area of constant pain, in addition to paresthesia and dysesthesia, there is an increase in the thresholds for injection and pain electrical stimulus. In patients with multiple sclerosis, who also suffer from attacks of painful paroxysms, sclerotic plaques were found in the afferents of the spinothalamic tract. Patients with thalamic pain that occurs after cerebrovascular disorders also have a decrease in temperature and pain sensitivity. At the same time, the lesions revealed by computed tomography correspond to the places of passage of somatic sensitivity afferents in the brainstem, midbrain, and thalamus. Spontaneous pain occurs in humans when the somatosensory cortex, which is the terminal cortical point of the ascending nociceptive system, is damaged.

Symptoms characteristic of neurogenic pain syndrome

Constant, spontaneous or paroxysmal pain, sensory deficit in the area of soreness, allodynia (the appearance of pain with a slight non-damaging effect: for example, mechanical irritation of certain skin areas with a brush), hyperalgesia and hyperpathia.

The polymorphism of pain sensations in different patients is determined by the nature, degree and location of the injury. With incomplete, partial damage to nociceptive afferents, acute periodic paroxysmal pain occurs more often, similar to an electric shock and lasting only a few seconds. In the case of complete denervation, pain is most often permanent.

In the mechanism of allodynia, great importance is attached to the sensitization of wide dynamic range neurons (WDD neurons), which simultaneously receive afferent signals from low-threshold "tactile" alpha-beta fibers and high-threshold "pain" C-fibers.

When a nerve is damaged, atrophy and death of nerve fibers occur (predominantly unmyelinated C-afferents die). Following degenerative changes, regeneration of nerve fibers begins, which is accompanied by the formation of neuromas. The structure of the nerve becomes heterogeneous, which is the reason for the violation of the conduction of excitation along it.

Zones of demyenylization and regeneration of the nerve, neuromas, nerve cells of the dorsal ganglia associated with damaged axons, are the source of ectopic activity. These loci of abnormal activity have been termed ectopic neuronal pacemaker sites with self-sustaining activity. Spontaneous ectopic activity is caused by instability of the membrane potential due to an increase in the number of sodium channels on the membrane. Ectopic activity has not only an increased amplitude, but also a longer duration. As a result, cross-excitation of the fibers occurs, which is the basis for dysesthesia and hyperpathia.

Changes in the excitability of nerve fibers during injury occur within the first ten hours and largely depend on axonal transport. Blockade of axotok delays the development of mechanosensitivity of nerve fibers.

Simultaneously with an increase in neuronal activity at the level of the posterior horns of the spinal cord, an increase in neuron activity was recorded in the experiment in the thalamic nuclei - ventrobasal and parafascicular complexes, in the somatosensory cortex of the cerebral hemispheres. But changes in neuronal activity in neurogenic pain syndromes have a number of fundamental differences compared to the mechanisms leading to sensitization of nociceptive neurons in patients with somatogenic pain syndromes.

The structural basis of neurogenic pain syndromes is an aggregate of interacting sensitized neurons with impaired inhibitory mechanisms and increased excitability. Such aggregates are capable of developing long-term self-sustaining pathological activity, which does not require afferent stimulation from the periphery.

The formation of aggregates of hyperactive neurons is carried out by synaptic and non-synaptic mechanisms. One of the conditions for the formation of aggregates in case of damage to neuronal structures is the occurrence of a stable depolarization of neurons, which is due to:

The release of excitatory amino acids, neurokinins and nitric oxide;

Degeneration of primary terminals and transsynaptic death of posterior horn neurons, followed by their replacement by glial cells;

Deficiency of opioid receptors and their ligands that control the excitation of nociceptive cells;

Increased sensitivity of tachykinin receptors to substance P and neurokinin A.

Of great importance in the mechanisms of formation of aggregates of hyperactive neurons in the structures of the central nervous system is the suppression of inhibitory reactions, which are mediated by glycine and gamma-aminobutyric acid. Deficiency of spinal glycinergic and GABAergic inhibition occurs with local ischemia of the spinal cord, leading to the development of severe allodynia and neuronal hyperexcitability.

During the formation of neurogenic pain syndromes, the activity of the higher structures of the pain sensitivity system changes so much that electrical stimulation of the central gray matter (one of the most important structures of the antinociceptive system), which is effectively used to relieve pain in cancer patients, does not bring relief to patients with neurogenic pain syndromes (PS).

Thus, the development of neurogenic BS is based on structural and functional changes in the peripheral and central parts of the pain sensitivity system. Under the influence of damaging factors, a deficiency of inhibitory reactions occurs, which leads to the development of aggregates of hyperactive neurons in the primary nociceptive relay, which produce a powerful afferent stream of impulses that sensitizes the supraspinal nociceptive centers, disintegrates their normal work and involves them in pathological reactions.

The main stages of the pathogenesis of neurogenic pain syndromes:

The formation of neuromas and areas of demyenization in the damaged nerve, which are peripheral pacemaker foci of pathological electrogenesis;

The emergence of mechano- and chemosensitivity in nerve fibers;

The appearance of cross-excitation in the neurons of the posterior ganglia;

Formation of aggregates of hyperactive neurons with self-sustaining activity in the nociceptive structures of the CNS;

Systemic disorders in the work of structures that regulate pain sensitivity.

anticonvulsants and drugs that enhance inhibitory reactions in the central nervous system-benzodiazepines;
GABA receptor agonists (baclofen, phenibut, sodium valproate, gabapentin (Neurontin);
calcium channel blockers, excitatory amino acid antagonists (ketamine, pheneclidine midantan lamotrigine);
peripheral and central Na-channel blockers.

PATHOPHYSIOLOGY OF PAIN SYNDROMES, PRINCIPLES

TREATMENTS (MESSAGE 1)

I.P. Nazarov

Krasnoyarsk State Medical Academy, rector - MD, prof.

I.P. Artyukhov; Department of Anesthesiology and Intensive Care № 1 IPO, head. -

MD, prof. I.P. Nazarov

Summary. The lecture deals with modern aspects of pathological pain: mechanisms, classification, distinctive features of the pathogenesis of somatogenic, neurogenic and psychogenic pain, primary and secondary hyperplasia, as well as features of their treatment.

Key words: pathological pain, classification, pathogenesis, treatment.

Mechanisms of pathological pain Every person in his life experienced pain - an unpleasant sensation with negative emotional experiences. Often pain performs a signaling function, warns the body of danger and protects it from possible excessive damage. Such pain is called physiological.

However, there is also pathological pain. This pain makes people unable to work, reduces their activity, causes psycho-emotional disorders, leads to regional and systemic microcirculation disorders, is the cause of secondary immune depression and disruption of the visceral systems. In a biological sense, pathological pain is a danger to the body, causing a whole range of maladaptive reactions.

There are five main components in the overall structure of pain:

1. Perceptual - allows you to determine the location of damage.

2. Emotional-affective - reflects the psycho-emotional reaction to damage.

3. Vegetative - associated with a reflex change in the tone of the sympathetic-adrenal system.

4. Motor - aimed at eliminating the effect of damaging stimuli.

5. Cognitive - participates in the formation of a subjective attitude to the pain experienced at the moment on the basis of accumulated experience.

According to time parameters, acute and chronic pain are distinguished.

Acute pain is new, recent pain that is inextricably linked to the injury that caused it. As a rule, it is a symptom of a disease. Disappears when damage is repaired.

Chronic pain often acquires the status of an independent disease. It goes on for a long period of time. The cause of this pain in some cases may not be determined.

Nociception includes 4 main physiological processes:

1. Transduction - the damaging effect is transformed in the form of electrical activity at the endings of sensory nerves.

2. Transmission - conducting impulses through the system of sensory nerves through the spinal cord to the thalamocortical zone.

3. Modulation - modification of nociceptive impulses in the structures of the spinal cord.

4. Perception - the final process of perception of transmitted impulses by a specific person with his individual characteristics, and the formation of a sensation of pain (Fig. 1).

Rice. 1. Basic physiological processes of nociception

Depending on the pathogenesis, pain syndromes are divided into:

1. Somatogenic (nociceptive pain).

2. Neurogenic (neuropathic pain).

3. Psychogenic.

Somatogenic pain syndromes occur as a result of stimulation of superficial or deep tissue receptors (nociceptors): in trauma, inflammation, ischemia, tissue stretching. Clinically, these syndromes are distinguished: post-traumatic, postoperative,

myofascial, pain with inflammation of the joints, pain in cancer patients, pain with damage to internal organs, and many others.

Neurogenic pain syndromes occur when nerve fibers are damaged at any point from the primary afferent conduction system to the cortical structures of the CNS. This may be the result of dysfunction of the nerve cell itself or of the axon due to compression, inflammation, trauma, metabolic disorders, or degenerative changes. Example: postherpetic, intercostal neuralgia, diabetic

neuropathy, rupture of the nerve plexus, phantom pain syndrome.

Psychogenic - in their development, the leading role is given to psychological factors that initiate pain in the absence of any serious somatic disorders. Often pains of a psychological nature arise as a result of overstrain of any muscles, which is provoked by emotional conflicts or psychosocial problems. Psychogenic pain may be part of a hysterical reaction or occur as a delusion or hallucination in schizophrenia and disappear with adequate treatment of the underlying disease. Psychogenic include pain associated with depression, which does not precede it and does not have any other cause.

According to the definition of the International Association for the Study of Pain (IASP - Intematinal Association of the Stady of Pain):

"Pain is an unpleasant sensation and emotional experience associated with or described in terms of actual or potential tissue damage."

Pathophysiological mechanisms of somatogenic pain syndromes

There are primary and secondary hyperalgesia.

Primary hyperalgesia covers damaged tissues. It is characterized by a decrease in pain threshold (BP) and pain tolerance to mechanical and thermal stimuli.

Secondary hyperalgesia is localized outside the damage zone. Has a normal BP and reduced pain tolerance only to mechanical stimuli.

Mechanisms of primary hyperalgesia

LIMBIC CORTEX

first order neurons

SOMATOSENSORY

enkephalins

periaqueductal gray matter

MIDBRAIN

nuclei of the medulla oblongata

Medulla

SPINOTHALAMIC TRACT

second order neurons

just look at n d y kinimi histamine

dorsal horns of the spinal cord enkephalins gammaaminobutyric acid noradrsialin

seroGONIM

Rice. 2. Scheme of nerve pathways and some neurotransmitters involved in nociception

Currently, great importance is given to bradykinin, which has a direct and indirect effect on sensitive nerve endings. The direct action of bradykinin is mediated through β-receptors and is associated with the activation of membrane phospholipase C. Indirect action: bradykinin acts on various tissue elements - endothelial cells, fibroblasts, mast cells, macrophages and neutrophils, stimulates the formation of inflammatory mediators in them (for example, prostaglandins), which , interacting with receptors on nerve endings, activate membrane adenylate cyclase. Adenylate cyclase and phospholipase C stimulate the formation of enzymes that phosphorylate ion channel proteins. As a result, the permeability of the membrane for ions changes - the excitability of nerve endings and the ability to generate nerve impulses are disturbed.

Sensitization of nociceptors during tissue damage is facilitated not only by tissue and plasma algogens, but also by neuropeptides released from C-afferents: substance P, neurokinin A, or calcitonin-gene-related peptide. These neuropeptides cause vasodilation, increase their permeability, promote the release of prostaglandin E2, cytokinins and biogenic amines from mast cells and leukocytes.

The afferents of the sympathetic nervous system also influence the sensitization of nociceptors and the development of primary hyperalgesia. The increase in their sensitivity is mediated in two ways:

1) by increasing vascular permeability in the area of damage and increasing the concentration of inflammatory mediators (indirect route);

2) due to the direct effect of norepinephrine and adrenaline (neurotransmitters of the sympathetic nervous system) on a2-adrenergic receptors located on the nociceptor membrane.

Mechanisms of development of secondary hyperalgesia

Clinically, the area of secondary hyperalgesia is characterized by an increase in pain sensitivity to intense mechanical stimuli outside the injury zone and can be located at a sufficient distance from the injury site, including on the opposite side of the body. This phenomenon can be explained by the mechanisms of central neuroplasticity leading to persistent hyperexcitability of nociceptive neurons. This is confirmed by clinical and experimental data indicating that the zone of secondary hyperalgesia persists with the introduction of local anesthetics into the area of damage and disappears in the case of blockade of the activity of neurons of the dorsal horn of the spinal cord.

Sensitization of neurons in the posterior horns of the spinal cord can be caused by various types of damage: thermal, mechanical,

due to hypoxia, acute inflammation, electrical stimulation of C-afferents. Great importance in the sensitization of nociceptive neurons of the posterior horns is given to excitatory amino acids and neuropeptides that are released from presynaptic terminals under the action of nociceptive impulses: neurotransmitters - glutamate, aspartate;

neuropeptides - substance P, neurokinin A, calcitonin-gene-related peptide and many others. Recently, nitric oxide (N0), which plays the role of an atypical extrasynaptic mediator in the brain, has been given great importance in the mechanisms of sensitization.

The sensitization of nociceptive neurons resulting from tissue damage does not need additional feeding with impulses from the site of damage and can persist for several hours or days even after the cessation of the receipt of nociceptive impulses from the periphery.

Thus, peripheral tissue damage triggers a cascade of pathophysiological and regulatory processes affecting the entire nociceptive system from tissue receptors to cortical neurons.

The most important links in the pathogenesis of somatogenic pain syndromes:

1. Irritation of nociceptors in case of tissue damage.

2. Algogen release and sensitization of nociceptors in the area of damage.

3. Strengthening of the nociceptive afferent flow from the periphery.

4. Sensitization of nociceptive neurons at various levels of the CNS.

In this regard, the use of agents aimed at:

1. suppression of the synthesis of inflammatory mediators - the use of non-steroidal and / or steroidal anti-inflammatory drugs (suppression of the synthesis of algogens, a decrease in inflammatory reactions, a decrease in the sensitization of nociceptors);

2. limiting the flow of nociceptive impulses from the area of damage to the central nervous system - various blockades with local anesthetics (prevent sensitization of nociceptive neurons, contribute to the normalization of microcirculation in the area of damage);

3. activation of the structures of the antinociceptive system - for this, depending on clinical indications, a whole range of drugs can be used that reduce pain sensitivity and negative emotional experience:

1) medications - narcotic and non-narcotic analgesics, benzodiazepines, a2-adrenergic agonists (clophelin, guanfacine) and others;

2) non-drug means - percutaneous

electrical nerve stimulation, reflexology, physiotherapy.

Perception

Tapmocorti-

projection

THALAMUS MODULATION

Local anesthetics Epidural, subdural, Into the celiac plexus

Local anesthetics Intravenous, intrapleural, intraperitoneal, in the incision area

transduction

Spinotdlamic

primary afferent receptor

impact

Rice. 3. Multilevel antinociceptive protection

Pathophysiological Mechanisms of Neurogenic Pain Syndromes Neurogenic pain syndromes occur when structures associated with the conduction of nociceptive signals are damaged, regardless of the location of damage to the pain pathways. The proof of this is

clinical observations. In patients after damage to the peripheral nerves in the area of constant pain, in addition to paresthesia and dysesthesia, there is an increase in the thresholds for injection and pain electrical stimulus. In patients with multiple sclerosis, who also suffer from attacks of painful paroxysms, sclerotic plaques were found in the afferents of the spinothalamic tract. Patients with thalamic pain that occurs after cerebrovascular disorders also have a decrease in temperature and pain sensitivity. At the same time, the lesions revealed by computed tomography correspond to the places of passage of somatic sensitivity afferents in the brainstem, midbrain, and thalamus. Spontaneous pain occurs in humans when the somatosensory cortex, which is the terminal cortical point of the ascending nociceptive system, is damaged.

Symptoms characteristic of neurogenic pain syndrome: persistent, spontaneous or paroxysmal pain, sensory deficit in the area of pain, allodynia (the appearance of pain with a slight non-damaging effect: for example, mechanical irritation

with a brush of certain skin areas), hyperalgesia and hyperpathia.

In the mechanism of allodynia, great importance is attached to the sensitization of neurons with a wide dynamic range (WDD-neurons), which simultaneously receive afferent signals from low-threshold "tactile" α-N-fibers and high-threshold "painful" C-fibers.

due to an increase in the number of sodium channels on the membrane. Ectopic activity has not only an increased amplitude, but also a longer duration. As a result, cross-excitation of the fibers occurs, which is the basis for dysesthesia and hyperpathia.

Release of excitatory amino acids, neurokinins and oxide

Degeneration of primary terminals and transsynaptic death of posterior horn neurons, followed by their replacement by glial cells;

Deficiency of opioid receptors and their ligands that control the excitation of nociceptive cells;

Increased sensitivity of tachykinin receptors to substance P and neurokinin A.

gamma-aminobutyric acid. Deficiency of spinal glycinergic and GABAergic inhibition occurs with local ischemia of the spinal

brain, leading to the development of severe allodynia and neuronal hyperexcitability.

Thus, the development of neurogenic BS is based on structural and functional changes in the peripheral and central parts of the pain sensitivity system. Under the influence of damaging factors, a deficiency of inhibitory reactions occurs, which leads to the development of aggregates of hyperactive neurons in the primary nociceptive relay, which produce a powerful afferent stream of impulses, the latter sensitizes the supraspinal nociceptive centers, disintegrates their normal work and involves them in pathological reactions.

The main stages of the pathogenesis of neurogenic pain syndromes

The formation of neuromas and areas of demyenization in the damaged nerve, which are peripheral pacemaker foci of pathological electrogenesis;

The emergence of mechano- and chemosensitivity in nerve fibers;

The appearance of cross-excitation in the neurons of the posterior ganglia;

Formation of aggregates of hyperactive neurons with self-sustaining activity in the nociceptive structures of the CNS;

Systemic disorders in the work of structures that regulate pain sensitivity.

Taking into account the peculiarities of the pathogenesis of neurogenic BS, it would be justified in the treatment of this pathology to use agents that suppress the pathological activity of peripheral pacemakers and aggregates of hyperexcitable neurons. Priority is currently considered: anticonvulsants and drugs that enhance inhibitory reactions in the central nervous system - benzodiazepines; GABA receptor agonists (baclofen, phenibut, sodium valproate, gabapentin (Neurontin); calcium channel blockers, excitatory amino acid antagonists (ketamine, pheneclidine midantan lamotrigine); peripheral and central Ka-channel blockers.

PATHOPHYSIOLOGY OF PAIN SYNDROME, PRINCIPLES OF

TREATMENT (MASSAGE 1)

I.P. Nazarov Krasnoyarsk state medical academy The modern aspecrs of pain pathology (mechanisms, classification, distinctive features of pathogenesis of somatogenic, neurogenetic and psychogenic pain, primary and secondary hyperplasia) and also methods of treatment are available in this article.