Pathophysiology of pain in inflammation. Pathophysiology of pain. pain syndromes. Etiology, pathogenesis of internal organs and tissues

Concept and general characteristics

Pain is a complex psycho-emotional unpleasant sensation, realized by a special system of pain sensitivity and higher parts of the brain. It signals the effects that cause tissue damage or already existing damage resulting from the action of exogenous factors or the development of pathological processes. The pain signal perception and transmission system is also called the nociceptive system2. Pain signals cause the corresponding adaptive effect - reactions aimed at eliminating either the nociceptive effect or the pain itself, if it is excessive. Therefore, under normal conditions, pain plays the role of the most important physiological defense mechanism. People with congenital or acquired (for example, due to injuries, infectious lesions) pathology of the nociceptive system, deprived of pain sensitivity, do not notice damage, which can lead to serious consequences. Various types of pain (acute, dull, localized, diffuse, somatic, visceral, etc.) are carried out by various structures of the nociceptive system.

pathological pain. In addition to the physiological pain described above, there is pathological pain. The main biological feature that distinguishes pathological pain from physiological pain is its maladaptive or direct pathogenic significance for the body. It is carried out by the same nociceptive system, but changed in pathological conditions and is an expression of a violation of the measure of the processes that realize physiological pain, the transformation of the latter from a protective one. into a pathological mechanism. The pain syndrome is an expression of the corresponding pathological (algic) system.

Pathological pain causes the development of structural and functional changes and damage in the cardiovascular system and internal organs, tissue degeneration, impaired autonomic reactions, changes in the activity of the nervous, endocrine and immune systems, psycho-emotional sphere and behavior. Severe and prolonged pain can cause severe shock, uncontrollable chronic pain can cause disability. Pathological pain becomes an endogenous pathogenic factor in the development of new pathological processes and acquires the significance of an independent neuropathological syndrome or even a disease. Pathological pain is poorly corrected, and the fight against it is very difficult. If pathological pain occurs a second time (with severe somatic diseases, with malignant tumors, etc.), then often, delivering excruciating suffering to the patient, it obscures the underlying disease and), becomes the main object of therapeutic interventions aimed at reducing the suffering of the patient.

Pathological pain of peripheral origin

This type of pathological pain occurs with chronic irritation of the recep-.,. pain tors (nociceptors), with damage to nociceptive fibers, spinal ganglia and posterior roots. These structures become a source of intense and often constant nociceptive stimulation. Nociceptors can be activated intensely and for a long time during chronic, inflammatory processes (for example, arthritis), under the action of tissue decay products (for example, with tumors), etc. Chronically damaged (for example, when squeezing scars, overgrown bone tissue and etc.) and regenerating sensory nerves, degeneratively altered (under the action of various hazards, with endocrinopathies), and demyelinated fibers are very sensitive to various humoral influences, even to those to which they do not respond under normal conditions (for example, to the action of adrenaline , K+ ions, etc.). Sections of such fibers become an ectopic source of constant and significant nociceptive stimulation.

A particularly significant role of such a source is played by a neuroma - a formation of chaotically overgrown, intertwined sensory nerve fibers, which occurs when they are disordered and difficult to regenerate. These endings are very sensitive to various mechanical, thermal, chemical and endogenous influences (for example, to the same catecholamines). Therefore, attacks of pain (causalgia) with neuromas, as well as with nerve damage, can be triggered by various factors and changes in the state of the body (for example, during emotional stress).

Nociceptive stimulation from the periphery can cause an attack of pain if it overcomes the so-called "gate control" in the posterior horns (Melzak, Wall), which consists of an apparatus of inhibitory neurons (neurons of the gelatinous substance play an important role in it), which regulates the flow of passing and ascending nociceptive stimulation. Such an effect can occur with intense stimulation or with insufficient inhibitory mechanisms of "gate control".

Pathological pain of central origin

This type of pathological pain is associated with hyperactivation of nociceptive neurons "at the spinal and supraspinal levels. Such neurons form aggregates that are generators of pathologically enhanced excitation. According to the theory of generator mechanisms of pain (G. N. Kryzhanovsky), GPUV is the main and universal pathogenetic mechanism pathological pain... It can form in various parts of the nociceptive system, causing the occurrence of various pain syndromes... When HPUV is formed in the posterior horns of the spinal cord, a pain syndrome of spinal origin occurs (Fig. 118), in the nuclei of the trigeminal nerve - trigeminal neuralgia (Fig. 119), in the nuclei of the thalamus - thalamic pain syndrome.The clinical picture of central pain syndromes and the nature of their course depend on the structural and functional features of those departments of the nociceptive system in which the HPUV arose, and on the characteristics of the GPUV activity.

In accordance with the developmental stages and mechanisms of HPSV activation in the early stages of the pathological process, an attack of pain caused by HPSV activation is provoked by nociceptive stimuli from a certain receptive field directly related to the HPSV (pain projection zone) (see Fig. 118, 119), at later stages, an attack is provoked by stimuli of different intensity and different modality, from different receptor fields, and can also occur spontaneously. The peculiarity of an attack of pain (paroxysmal, continuous, short-term, prolonged, etc.) depends on the features of the functioning of the GPUV. The nature of the pain itself (dull, acute, localized, diffuse, etc.) is determined by what formations of the nociceptive system, realizing the corresponding types of pain sensitivity, have become parts of the pathological (algic) system underlying this pain syndrome. The role of the pathological The determinant that forms the pathological system of this syndrome is played by the hyperactive formation of the nociceptive system, in which the primary HPUV arose.For example, in pain syndrome of spinal origin, the role of the pathological determinant is played by the system of hyperactive nociceptive neurons of the posterior horn (I-III or/and V layer).

GPUV in the central apparatus of the nociceptive system is formed under the influence of various factors. It can occur with prolonged nociceptive stimulation from the periphery. Under these conditions, pain originally of peripheral origin acquires a central component and becomes a pain syndrome of spinal origin. This situation occurs in chronic neuromas and damage to the afferent nerves, in neuralgia, in particular in trigeminal neuralgia.

HPUV in the central nociceptive apparatus can also occur during deafferentation, due to an increase in the sensitivity of deafferented nociceptive neurons and impaired inhibitory control. Deafferentation pain syndromes can appear after amputation of limbs, transection of nerves and posterior roots, after a break or transection of the spinal cord. In this case, the patient may feel pain in a devoid of sensitivity or in a non-existent part of the body (for example, in a non-existent limb, in parts of the body below the spinal cord transection). This type of pathological pain is called phantom pain (from phantom - a ghost). It is due to the activity of the central GPUV, the activity of which no longer depends on nociceptive stimulation from the periphery.

HPV in the central parts of the nociceptive system can occur with infectious damage to these parts (herpetic and syphilitic lesions, trauma, toxic effects). In the experiment, such HPUV and the corresponding pain syndromes are reproduced by introducing into the corresponding parts of the nociceptive system substances that either cause a violation of inhibitory mechanisms or directly activate nociceptive neurons (tetanus toxin, penicillin, K+ ions, etc.).

In the central apparatus of the nociceptive system, secondary HPVs can form. So, after the formation of HPSV in the posterior horns of the spinal cord, after a long time, a secondary HPSV can occur in the thalamus. Under these conditions, the primary HPUV may even disappear, however, the projection of pain to the periphery may remain the same, since structures of the same nociceptive system are involved in the process. Often, when the primary HPSV is localized in the spinal cord, in order to prevent the receipt of impulses from it to the brain, a partial (break in the ascending tracts) or even complete transection of the spinal cord is performed. This operation, however, has no effect or causes only a short-term relief of the patient's suffering.

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 degeneration, 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.

Central sources of pathological pain. Prolonged and sufficiently intense nociceptive stimulation can cause the formation of a generator of pathologically enhanced excitation (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. 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, 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.

A prerequisite for the formation and operation of the GPU is 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 turns into a generator that generates an intense and prolonged stream of impulses.

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. A prerequisite Insufficient inhibition of the neurons of this system is the cause of the emergence and functioning of the painful HPS in any link of the nociceptive system.

Causes The occurrence of HPSV in the nociceptive system may be a partial deafferentation of neurons, for example, after a break or damage to the sciatic nerve or posterior roots. Under these conditions, epileptiform activity is recorded electrophysiologically, initially in the deafferent 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. 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. 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.

131 (private). 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 system is represented by formations of the spinal cord and brain, where the relay functions of nociception are carried out. 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 the posterior horns. Crossed and non-crossed axons of these neurons form spinothalamic tract occupying the anterolateral regions of the white matter of the spinal cord. In the spinothalamic tract, neospinal (located laterally) and paleospinal (located medially) portions are isolated. AT the thalamus contains a third neuron whose axon reaches the somatosensory zone 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) occurs when damage or irritation of both peripheral nerve structures (nociceptors, peripheral nociceptive fibers) and central (synapses at different levels of the spinal cord, medial trunk loop, including the thalamus, internal capsule, cerebral cortex ). Pathological pain occurs due to the formation of a pathological algic system in the nociceptive system.

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 (direct electrical stimulation of certain brain structures). 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 serotonergic and noradrenergic neurons, which 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 a focus of increased excitation 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.

Question 132. Pavlov's teaching on neurosis. Etiology and mechanisms of the formation of neurotic states. Neurosis as a predisease Under neurosis, IP Pavlov understood a long-term disturbance of higher nervous activity caused by an overstrain of nervous processes in the cerebral cortex by the action of external stimuli inadequate in strength or duration. In the Pavlovian concept of neurosis, firstly, the psychogenic occurrence of a breakdown of higher nervous activity is essential, which outlines the boundaries between neuroses and reversible disorders of a non-psychogenic nature, and secondly, the relationship of clinical forms of neuroses with types of higher nervous activity, which allows us to consider the classification of neuroses not only with clinical, but also from a pathophysiological point of view. There are 3 classical forms of neuroses: neurasthenia, hysteria (hysterical neurosis) and obsessive-compulsive disorder. Psychasthenia is discussed in the section on psychopathy. NEURASTHENIA- the most common form of neuroses; pronounced weakening of the nervous system as a result of overstrain of the irritable or inhibitory process or their mobility. Clinical picture- a state of irritable weakness: a combination of increased irritability and excitability with increased fatigue and exhaustion. 3 stages (forms) of neurasthenia. The initial stage is characterized violation of active inhibition, manifested mainly by irritability and excitability - the so-called hypersthenic (irritative) neurasthenia. In the second, intermediate stage when the lability of the excitatory process appears, irritable weakness predominates. In the third stage (hyposthenicneurasthenia) with the development of protective inhibition, weakness and exhaustion, lethargy, apathy, increased drowsiness, and low mood predominate. HYSTERIC NEUROSIS- a group of psychogenic neurotic conditions with somatovegetative, sensory and motor disorders, is the second most common form of neurosis, is much more common at a young age, and much more often in women than in men, and especially easily occurs in people suffering from hysterical psychopathy. Clinical picture: extremely variegated, polymorphic and variable symptoms are schematically divided into mental disorders, motor, sensory and vegetative-visceral disorders. For movement disorders hysteria includes convulsive seizures, paresis, paralysis, including astasia-abasia, which is very characteristic of hysteria, hyperkinesis, contractures, mutism, hysterical stupor, etc. Of sensory disturbances the most typical are hysterical blindness, deafness (aphonia), and sensory disturbances in the form of hypesthesia, hyperesthesia, and paresthesia. Vegetative-somatic disorders in hysterical neurosis, they manifest themselves in violations of breathing, cardiac activity, the gastrointestinal tract, and sexual function. NEUROSIS OF OBSESSIVE CONDITIONS combines various neurotic states with obsessive thoughts, ideas, ideas, drives, actions and fears; occurs much less frequently than neurasthenia and hysterical neurosis; in men and women it is observed with the same frequency. I. P. Pavlov pointed out the need to distinguish psychasthenia as a special temperament from obsessive-compulsive neurosis (“compulsive neurosis”). clinical picture. Obsessive-compulsive disorder occurs more easily in persons of the mental type (according to I. P. Pavlov), especially when the body is weakened by somatic and infectious diseases. Obsessive phenomena are very numerous and varied, most typical phobias as well as obsessive thoughts, memories, doubts, actions, drives. More common are cardiophobia, cancerophobia, lyssophobia (obsessive fear of insanity), oxyphobia (obsessive fear of sharp objects), claustrophobia (fear of enclosed spaces), agoraphobia (fear of open spaces), obsessive fears of heights, pollution, fear of blushing, etc. Obsessive phenomena are irresistible and occur against the wishes of the patient. The patient treats them critically, understands their strangeness, seeks to overcome them, but cannot get rid of them on his own. According to the features of the flow, 3 types are distinguished: the first - with a single attack of the disease which can last weeks or years; the second - in the form of relapses with periods of full health; third - continuous flow with occasional aggravation of symptoms. Obsessive-compulsive disorder, unlike neurasthenia and hysterical neurosis, is prone to a chronic course with exacerbations, usually psychogenic.

The mechanisms of regulation of pain sensitivity are diverse and include both nervous and humoral components. The laws governing 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 certain 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, in the development of pain reaction an important role is played by the so-called substance pi. It is found in large quantities in the neurons of the posterior 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 posterior 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 for 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, increasing presynaptic inhibition in the somatic and visceral afferent systems.

Pain is defined as a multicomponent psychophysiological state of a person, including: 1) own feeling of pain; 2) certain autonomic reactions (tachycardia, changes in blood pressure); 3) emotional component (negative emotions: sthenic and asthenic (depression, fear, melancholy); 4) motor manifestations (avoidance reflex - hand withdrawal); 5) volitional efforts (psychogenic setting - a decrease in the severity of pain sensation).

Pain classification:

I. By origin:

• A) "Physiological" - caused by a certain external influence;
• - depends on the strength and nature of the stimulus (adequate to it);
• - mobilizes the body's defenses;
• - is a signal of danger (possibility of damage).
• B) Pathological = neuropathic - caused by nerve damage. systems;
• - not adequate to a certain impact;
• - does not mobilize the body's defenses
• - is a signal of pathology, characteristic of diseases of the nervous system.

II. According to the localization of nociceptors and the nature of pain sensations:

• 1. Somatic:
  • a) superficial:
    • - epicritical (early, fast);
    • - protopathic (late, slow).
  • b) deep.
• 2. Visceral: (associated with Zakharyin-Ged zones)
• a) true;
• b) reflected.

Somatic pain is associated with damage to the skin, muscles, ODA in general.

Superficial pain occurs when irritation of nociceptors of the skin,

Epicritical (early) pain is called rapid because:

occurs in a fraction of a second;

has a short latent period;

precisely localized;

passes quickly;

sharp, transient sensation.

Protopathic (late) pain is characterized by:

longer latent period (several seconds);

more diffuse;

longer;

accompanied by an unpleasant sensation of pain.

This separation is associated with the conduction of excitation - along myelin fibers A (rapid pain); along unmyelinated fibers C (slow pain).

Group A fibers are thick myelin fibers (V wire 50-140 m / s).

Group B fibers - smaller diameter, B1 and B2 (V wire 15-30; 10-15 m / s).

Fibers C - unmyelinated - of smaller diameter (V=0.6-2 m/s).

Unmyelinated fibers are more resistant:

• - to hypoxia (because the activity of metabolism is reduced);
• - regenerate faster;
• - characterized by a more diffuse distribution of fibers in the zone of innervation.

When nerve fibers are compressed, myelinated fibers are the first to suffer, the anesthetic during anesthesia will act more quickly on unmyelinated fibers.

Deep pain is associated with irritation of deep tissue receptors (tendons, bones, periosteum).

The nature of the pain: - dull;

• - aching;
• - long;
• - diffuse;
• - prone to irradiation.

Causes of deep pain:

• - tissue stretching;
• - strong pressure on the tissue;
• - ischemia;
• - the action of chemical irritants.

Visceral pain - occurs when the receptors of internal organs are irritated.

Character of pains: - dull;

• - aching;
• - painful;
• - long;
• - high ability to irradiation.

Causes of visceral pain:

• - stretching of hollow organs;
• - spastic contractions of hollow organs;
• - stretching (spastic contraction of the blood vessels of the organs);
• - ischemia;
• - chemical irritation of the membranes of organs (with PU);
• - strong contraction of organs (contraction of the intestines).

The main mechanisms of pain formation.

Pain is the result of the interaction of two systems: pain (algic, nociceptive), analgesic (analgesic, antinociceptive).

The pain system includes 3 links:

Receptor.

Conductor link.

Central link.

Receptors: According to modern concepts, special, highly differentiated receptors are designed to perceive various modalities.

Pain receptor groups:

Mechanical

Especially for the perception of fast damaging stimuli (the action of sharp objects), generate epicritical pain, associated with A fibers, less with C fibers.

Damage with a sharp object tension of the receptor activation of ion channels input of Na excitation of the receptor.

Polymodal

• - associated with C fibers, less with A fibers, perceive the action of stimuli of more than 1 modality with a damaging energy value:
  • a) mechanical stimuli of damaging value (pressure);
  • b) heating of damaging value;
  • c) some chemical irritations (capsaicin - a substance of red pepper, bradykinin).

The mechanism of receptor activation is associated with both the activation of ion channels and the activation of second messengers.

Thermal receptors

• - bound to C fibers, activated by special cation channels tuned to the gradation temperature; perceive both thermal and cold damaging effects.
• 4) Silent receptors
• - under normal conditions, they are not involved in the process, they are activated during the inflammatory process. For example: bradykinin, Pg - increase the sensitivity of receptors, therefore, with inflammation, pain sensations intensify - the phenomenon of peripheral sensitization.

According to modern concepts, 2 mechanisms are distinguished

nociceptor activity:

Primary - occurs at the site of damage due to the fact that cell destruction is accompanied by an increase in the number of K + ions, the formation of Pg, bradykinin, the thresholds of polymodal receptors are lowered, their activation and the appearance of impulses going to the central nervous system. In inflammation, the role of pain mediators can also be played by LT, IL-1, IL-8, TNFOL.

Secondary - an impulse from the nerve is conducted not only in the central nervous system, but also in parallel, along other terminals, retrograde (i.e. back to the site of damage). Substance P is secreted at the ends of these terminals.

Its effects:

Vasodilation;

Activation of mast cells release of histamine irritation of nociceptors;

Activation of platelets, release of serotonin, activation of nociceptors.

The conductive part - the excitation goes along the sensory fibers to the posterior horns, where the excitation switches to the second neuron of the path.

There are 2 options available:

With normal, not too frequent impulses, β-glutamate is released in the endings, which activates propionate-containing receptors of 2 neurons, fast pain.

Frequent impulses along the afferent pathway release of neurotransmitters - glutamate and substance P activation of the neuron containing aspartate receptor 2 slow and severe pain (this is the phenomenon of central pain sensitization).

Visual hillocks - 3rd neuron of the path - from here the excitation rises to the corresponding sensory zone of the cerebral cortex. Activation of the reticular formation is necessary for the sensation of pain formation. Collaterals of the pain pathway rise into the structures of the limbic system - the emotional coloring of pain.

Excitation of the cortical zone is necessary for the awareness of pain and its precise localization.

The first sensation of pain is indefinite, undifferentiated, but very painful. It arises due to the excitation of the nuclei of the visual tubercles - thalamic pain between the visual tubercles and the cortical zone, due to the inclusion of nonspecific thalamic nuclei, circulation of excitation occurs = reverbation.

Antinociceptive system (AS)

includes 2 departments:

Certain centers of the brain with a descending antinociceptive pathway;

Segmental mechanisms or mechanisms of sensory pain flow at the entrance (gate mechanisms).

A.S., giving a descending path, has centers - this is a gray matter surrounding the Sylvian aqueduct (peripheral gray matter), some suture nuclei; gray matter adjacent to the walls of the third ventricle and the median anterior cerebral bundle in the central part of the hypothalamus.

The first efferent fibers (enkephalin-secreting fibers) descend from the gray matter, they end in the raphe nuclei. The next neuron - (2) - is a neuron of the raphe nuclei (serotonergic) - these fibers end in the posterior horns of the spinal cord on the 3rd neuron of the descending pathway (enkephalinergic), the 3rd neuron forms synapses on the presynaptic terminals of the afferent neuron.

Effects of enkephalin:

Decreased potential amplitude on presynaptic membranes.

Decreased secretion of the mediator of the pain pathway (-glutamate, substance P).

Inhibition/blocking of pain impulses due to presynaptic inhibition.

Segmental mechanisms of pain:

The basis of the gate mechanism of pain flow regulation is the interaction between pain impulses and impulses along the pathways of tactile, temperature sensation through neurons (SG) of a gelatinous substance.

These neurons are excited by the flow of temperature and tactile sensitivity and cause presynaptic inhibition of the second pain pathway neuron.

Among the neurons of A.S. many neurons secreting opioid peptides (enkephalins, leu- and met-) and endorphins (29-31 AK).

Previously, opiate receptors were discovered, i.e. receptors that interact with morphine (foreign alkaloid).

Opioid peptides and their receptors are distributed in different areas of the brain (hypothalamus, limbic system, cerebral cortex).

Main effects of opioid peptides:

Play the role of neurotransmitters A.S.

Excite the pleasure center, cause a feeling of euphoria.

They are modulators (adapt the body).

They are components of the anti-stress system or the stress-limiting system.

Special types of pain:

projected pain

When the nerve trunk is damaged, a sensation of pain occurs in the corresponding area of ​​​​the body surface, although this area is not irritated.

Mechanism: due to the body scheme rigidly fixed in the cortical representation.

neuralgia

• - pain associated with damage to the nerve trunks.
• 3) Causalgia
• - excruciating, persistent pain that occurs with incomplete damage to the sensory fibers of the nerve trunks, including sympathetic nerve fibers. The excitation of pain fibers often occurs according to the mechanism of artificial synapses (ephaps) - incomplete damage to the nerve trunks and the appearance of damage currents.
• 4) Phantom pains
• - Pain in the amputated limb.
• 2 hypotheses of their development:
• 1. Increased impulsation from the stump of a cut or torn nerve to pain corresponding to the projection in the cortex of any zone.
• 2. Persistent circulation of excitation between the thalamus and the cortical zone - the projection of the amputated part of the body is excited.
• 5) Reflected pain
• - Zakharyin-Ged zones.

Mechanism: It is based on the principle of innervation of each segment of the body from the corresponding segment of the spinal cord.

• 2 hypotheses:
• 1. Convergence hypothesis of paths.
• -is based on the phenomenon of excitation summation on the second neuron.
• 2. Facilitation hypothesis.

Topic 3. Pathology of motor functions of the CNS

Classification:

Weakening of motor functions up to complete loss (paresis, paralysis).

Increased motor function (hyperkinesia).

Ataxia (impaired coordination of movements at rest and during movement).

Paresis or paralysis appears when the pyramidal system is damaged, which provides precise, finely coordinated movements, incl. and acquired motor skills (writing).

Central paralysis develops with:

damage to the body of the pyramid.

damage to cortical fibers.

Peripheral paralysis develops with:

damage to the body-motor neuron.

damage to its fibers.

Signs of central paralysis:

Loss of voluntary movements on the opposite side of the body.

Hypertonicity in the corresponding muscles.

Clonus - rhythmic contractions of the limb with a sharp sudden irritation.

Preservation and strengthening of tendon reflexes on the damaged side.

There is no violation of muscle trophism.

Weakening or cessation of surface reflexes.

There are 2 main regulatory systems:

• 1) Pyramidal system.
• 2) Extrapyramidal system.

Preservation of hypertonicity and tendon reflexes occurs because the tendon reflexes are spinal, and the arc of the spinal reflex is preserved, so they persist with central paralysis. There is no muscle dystrophy and atrophy, because the muscle nerve is not disturbed, the g-motoneuron innervates the contractile elements of the intrafusal fiber.

Tendon reflex amplification mechanisms:

Increased excitation of the g-motor neuron of the spinal cord due to the cessation of descending supraspinal influences, mainly inhibitory, increased contraction of the muscle elements of the intrafusal fiber and increased stretching of the annulospinal endings, increased afferent flow to the motoneurons, increased muscle contraction hypertonicity.

Clonus is the result of increased tendon reflexes with increased recoil effects.

The weakening of skin reflexes is the result of damage to sensory neurons scattered in areas of the motor cortex, as well as possible damage to the sensory zone.

The Babinski reflex is the result of a violation of supraspinal influences (fan-shaped divergence of the toes in response to dashed irritation).

Signs of peripheral paralysis:

Absence of voluntary movements in a separate limb corresponding to the damaged segment.

Absence of tendon reflexes, tk. the reflex arc is damaged.

Hypotension of the muscles as a result of loss of influence from the proprioreceptors of the muscle spindles.

Muscle atrophy / dystrophy as a result of its denervation and disruption of its connection with the trophic center.

Changes in the excitability of muscle tissue, incl. violation of the electrical excitability of tissues (an increase in rheobase and an increase in the duration of chronoxia).

Brown-Sequard Syndrome:

(when transection of the right or left half of the spinal cord).

Disorder of pain and temperature sensitivity on the opposite side.

Disorder of deep and tactile sensitivity on the side of damage.

Motor disorders of the type of central paralysis on the side of the spinal cord injury.

Hyperkinesis.

Excessive, violent movements that do not obey the will of a person, unusual, pretentious.

Classification (depending on origin):

Spinal.

Pyramidal.

Extrapyramidal.

• 1. Spinal (convulsions) - twitching (fascilation) of the muscles. They are not accompanied by movement of the limb as a whole.
• 2. Pyramidal (convulsions):

By nature: - clonic;

Tonic.

Clonic - characterized by rapid alternating contraction and relaxation of muscle groups, they can be caused by a point touch on the motor cortex.

Tonic - slow contractions of muscle groups and body parts, and the body can freeze in an unusual position, due to the simultaneous contraction of antagonist muscles. It is believed that tonic convulsions arise as a result of a violation of cortical influences on subcortical formations, on the basal ganglia, i.e. on the elements of the extrapyramidal system.

Seizures in themselves are not painful, they are symptoms that occur in various diseases, accompanied by a violation of the functions and interactions of brain structures.

Seizures are primary (idiopathic; genuin epilepsy) and secondary (with various diseases: fever in children, alkalosis, infectious and inflammatory diseases of the brain, trauma > formation of glial scars > occurrence of post-traumatic epilepsy).

General mechanisms of the pathogenesis of seizures:

Neurotransmitter imbalance.

Direct stimulation of neurons during scar formation.

Weakening of inhibition in the CNS.

Change in electrolyte balance.

The common link in pathogenesis is the formation of a population of hyperactive neurons.

Individual predisposition to seizures is different.

• 3. Extrapyramidal (convulsions).
• a) chorea.
• b) Athetosis.
• c) Parkinson's disease.
• d) Ballism.

Associated with damage to the extrapyramidal system (EPS).

EPS is an extensive system of nuclei and pathways.

• 1) Basal ganglia: striopallidar system - caudal nucleus; putamen (pillow); pale ball.
• 2) Black substance.
• 3) Lewis kernel.
• 4) Red core.
• 5) Reticular formation of the brain stem.
• 6) Vestibular nuclei.

The downward path is represented by paths:

Reticulospinal.

Rubrospinal.

Vestibulospinal.

• a) chorea.
• 1) It occurs when the neostriatum is damaged, a decrease in GABA secretion, disinhibition of the substantia nigra (SN), an increase in dopamine production, inhibition of the neostriatum, hypotension.
• 2) Damage to the caudal nucleus and putamen (pillows), rupture of the feedback ring, disinhibition of the premotor cortex hyperkinesis.

The nature of hyperkinesis:

• - contraction of the proximal parts of the limbs and facial muscles grimacing, sometimes acquired (rheumatism in childhood) and hereditary (congenital - Hutchington's chorea).
• b) Athetosis.

Occurs when the lateral part of the pale ball is damaged. Hyperkinesias are in the nature of worm-like movements of the limbs and torso, as a result of contraction of the antagonist muscles of the distal muscle groups and elements of plastic tone.

c) ballism.

It is characterized by movement of limbs such as threshing (flexion, extension).

d) Parkinson's disease.

Occurs with primary damage to the substantia nigra (SN).

• 1. Damage to SN, decrease in dopamine release, disinhibition of the striopallidary system, increase in descending influences on motor neurons, increase in muscle tone, rigidity.
• 2. Symptom of "Gear Wheel".
• 3. Akinesia manifests itself as a special difficulty in starting a movement, the movements are slow with the absence of additional movements in the motor complexes.
• 4. Masked face.
• 5. Tremor (tremor paralysis). It manifests itself at rest, characterized as a rapid alternation of antagonist muscles in the distal sections.

The tremor is based on increased excitation of the striopallidary system, because inhibitory influences are weakened, but active cortical influences remain, there is a breakthrough of excitation into the premotor zone of the cortex, there are no hyperkinesis due to increased rigidity.

Cerebellar tremor - dynamic.

This is a violation of coordination of movements when standing and walking.

Types of ataxia:

• 1) Spinal - impaired afferentation from proprioreceptors.
• 2) Cerebral (frontal) - with cortical damage.
• 3) Cerebellar.
• 4) Labyrinth - in violation of balance control.

Ataxia can be static (when standing) or dynamic (when walking).

Topic 4. Pathophysiology of GNI

GNI is the behavior of a trained person, combining innate behavioral acts (instincts) and learning.

GNI is based on higher brain functions:

Perception.

Attention.

Ability to learn.

Speech. autonomic nervous disorder pain

At the heart of the pathology of VND is a violation of the higher functions of the brain and subcortical structures.

Violations of the GNI can be the result of functional disorders (the dynamics of nervous processes in certain parts of the brain); can be organic, as a result of damage to various parts of the brain.

A classic example of functional disorders.

Neuroses are psychogenic, neuropsychiatric disorders that have arisen as a result of a violation of the interaction of a person with the external environment, when the requirements of the external environment exceed the capabilities of a person and manifest themselves in certain clinical symptoms, but without psychotic disorders (without symptoms).

Neurosis is a personality disease that has arisen as a result of a person's conflict with the external environment.

Etiology:

Excessive neuropsychic overstrain:

• a) social problems
• b) personal troubles (production activity),
• c) intimate troubles (unhappy love),
• d) extreme conditions (wars, earthquakes).

There are 3 concepts of the origin of neuroses, there is a connection between specific circumstances and the result of excessive stress.

Theories of neuroses:

Biological (Peter Kuzmich Anokhin).

The reason for the psycho-emotional stress of a person is the mismatch between the planned achievement and the real result. The more important is the goal, the motive of the action, the more stress this mismatch causes.

II. Informational (Pavel Vasilyevich Simonov).

The main reason for excessive stress is the lack of necessary information, especially against the background of redundant, unnecessary information.

The formula for the degree of neuropsychic stress:

n - necessary: ​​information, time, energy;

c - existing: information, time, energy.

The more important the ultimate goal and the greater the difference between real and necessary conditions, the greater the degree of nervous strain.

Degrees of neuropsychic stress:

Mobilization of attention, human activity, increase in MS.

An increase in tension until the appearance of emotional accompaniment (active sthenic negative emotions arise - anger, rage, aggression).

Development of asthenic negative emotions (fear, depression, melancholy).

These 3 degrees of neuropsychic stress are reversible and when the traumatic situation is eliminated, everything returns to normal.

The occurrence of neurosis, which already requires special treatment.

Sh. The theory of deficit of adaptive energy - volitional energy = deficit of social communication during the formation of a person.

Predisposed to neurosis - children growing up in isolation from their peers.

Risk factors for the development of neuroses:

Age (young men, elderly people - increased asthenization of the nervous system due to endocrine changes).

Nutrition (there must be a sufficient amount of protein in food, especially in the first 3 years of life, protein deficiency irreversible changes in the brain and GNI).

Hypodynamia (decrease in excitability and brain activity, because:

• a) decrease in impulses to the brain, activation through the reticular formation of the brain stem;
• b) restriction of blood supply to the brain due to detraining of the myocardium;
• c) cerebral hypoxia).
• 4) Smoking, alcohol.
• 5) The work of a person associated with increased overvoltage (people of mental labor).
• 6) Changing living conditions (urbanization of the population).
• 7) A certain type of GNI (both biological and personally human).

The type of GNI is an important natural characteristic of a person, which is based on the properties of nervous processes.

Principles of GNI classification:

The ratio of nervous processes and their properties:

strength - balance - mobility

For the first time, the conditioned reflex method (objectification of nervous processes) was proposed by I.P. Pavlov:

The main 4 types are identified, which are comparable with the classification of Hippocrates' temperaments.

Temperament is a naturally determined characteristic of a person, including the dynamic properties of the psyche, which are manifested in all human reactions.

Temperament was later described by Kant, Galen.

• * 1 type according to Pavlov - a strong unbalanced type with a predominance of excitation (choleric according to Hippocrates).
• Type 2 according to Pavlov - strong, balanced, mobile (sanguine).
• Type 3 according to Pavlov - strong, balanced, inert (phlegmatic).
• *4 type according to Pavlov - weak type (melancholic).
• * - hereditary predisposition to the occurrence of neuroses.
• 2) Actually human types of GNI.
• 1 principle - general biological types.

Human types - a reflection of the outside world by a person, which depends on 1 and 2 signaling systems.

• a) sensory - good development of 1 signal system, imagery, eloquence of human thinking.
• b) abstract - a good development of the 2nd signal system, the conceptual apparatus is widely used in thinking.

Depending on the ratio of 1 and 2 of the signal system, there are:

• 1) artistic (artistic type).
• 2) thinking (abstract type).
• 3) mixed (medium type).

If the predisposition to the development of neuroses depends on the naturally determined biological type, then the clinical form depends on the specific human type of GNA.

The main clinical forms of neurosis:

Neurasthenia.

Obsessional neurosis.

It develops in people of a mixed type, associated with prolonged overwork, mental traumatization.

• 1. Hypersthenic - increased reactivity, irritability (flares up quickly, burns out quickly).
• 2. Hyposthenic - a decrease in the strength of nervous processes.
• 3. Asthenic - weakening of nervous processes, adynamism, etc.

Occurs in people of an artistic type with reduced intelligence. It is characterized by increased human demands on the environment, demonstrative behavior; sensory disturbances to complete blindness and deafness; motor disorders; autonomic reactions from the cardiovascular system (arrhythmias, changes in blood pressure).

Arise in people with a predominance of conceptual thinking. This neurosis is manifested by phobias, anxiety, ritual actions; nosophobia.

Pathophysiological aspects of GNI disturbance in neuroses:

Violation of excitation processes.

Violation of the processes of inhibition.

Types of neuroses.

2 types depending on the disturbance of processes: 1) excitation, 2) inhibition and 3) mobility of nervous processes.

Reasons for getting neuroses:

The use of excessive stimuli.

Mechanism: overvoltage of excitation processes.

Strengthening the action of inhibitory stimulation.

Mechanism: overvoltage of braking processes.

Overstrain of the mobility of nervous processes (alteration of the signal value of the stimulus).

Simultaneous use of positive and negative stimuli “crosslinking” of nervous processes, impaired mobility and balance of processes.

Development of complex differentiation (comparison of a circle and an ellipse).

The pathogenesis of neurosis:

Asthenization of nerve cells - a decrease in PC.

Reducing the strength of the processes of inhibition and excitation.

Violation of the balance of processes.

Disturbance of mobility of nervous processes:

• a) with increased mobility (increased lability of processes);
• b) with a decrease in mobility (increased inertia).
• 5) Development of phase phenomena (see parabiosis).
• 6) Autonomic disorders (disorders of the cardiovascular system).

Treatment of neuroses.

Eliminate mental trauma.

Drug correction of nervous processes (tranquilizers, sedatives, sleeping pills).

Proper mode of work and rest.

Secondary neuroses (somatogenic) - neuroses arising under the influence of somatic diseases.

The mechanism of development of somatogenic neuroses:

Adverse effect of the disease itself (psychogenic).

Unusual afferent impulses from the affected organs (pain impulses and chronic pain).

Violation of the delivery of essential nutrients to the brain tissue, O2 hypoxia, malnutrition.

Topic 5. Pathology of the autonomic nervous system

Sympathetic Nervous System (Senior Researcher);

Parasympathetic nervous system (p.s.n.s.).

The sympathetic nervous system is ergotropic, because sympathetic activation carries out a universal catabolic effect, provides energy supply for the body's activity and efficient use of energy.

ANS - 2 neurons, neurons are interrupted in the autonomic ganglia.

Preganglial fibers - short, postganglial fibers - long diffuse nature of the distribution of fibers generalized reactions. The secreting features of the preganglial nerve fibers are all cholinergic.

Postganglial fibers are mostly adrenergic and secrete norepinephrine, except for the sweat glands and some vascular membranes (cholinergic).

S.S. Effects:

• - stimulation of the cardiovascular system,
• - expansion of the bronchi, etc.

The parasympathetic nervous system is trophotropic, because stimulates the processes of anabolism and restoration of reserves and forms a depot of nutrients.

Preganglionic fibers (from the craniobulbar and sacral sections) in the organs switch in the intramural ganglia, postganglionic fibers are short > local parasympathetic reactions (cholinergic).

P.S. effects n.s.:

Opposite s.s.s.

There are mutually activating influences between the sympathetic and parasympathetic divisions of the nervous system.

The sympathetic nervous system maintains activation

parasympathetic division through the following mechanisms:

Central.

Reflex.

Peripheral.

• a) increased energy metabolism in all nerve centers;
• b) suppression of cholinesterase activity;
• c) increase in the content of Ca2+ in the blood; activation of p.s. centers.

Increased blood pressure sympathetic effect increased irritation of baroreceptors increased tone of the vagus nerves.

Main: suppression of cholinesterase activity, destruction of ACh.

The parasympathetic nervous system activates

sympathetic department through the following mechanisms:

Reflex activation from reflexogenic zones.

Peripheral mechanisms of excess K+ ions.

It is believed that the metabolic products A and HA (adrenochromes) have vagotropic activity.

The interaction of systems provides a certain balance of sympathetic and parasympathetic effects, but this balance can be disturbed, in the direction of the predominance of one or another system.

Disorders of ANS functions include:

Functional disorders associated with changes in the state of the centers.

Peripheral disorders - damage to nerve fibers.

Centrogenic disorders (damage to the diencephalic region of the brain).

See Zaiko's tutorial.

Allocate an increase in the tone of the vegetative centers and a violation of their excitability (tonicity).

The main violations of tone:

Sympathotonia - an increase in the tone of sympathetic centers, accompanied by an increase in efferent impulses and a massive release of mediators. At the same time, an increase in the synthesis of mediators is not accompanied by an increase in the synthesis of enzymes that destroy it; a prolonged action of mediators is tonicity.

Vagotonia - an increase in the tone of the parasympathetic centers.

Amphotonia - an increase in the tone of both centers.

Sympathoergy - an increase in the excitability of the sympathetic department, the reactions are enhanced, but short-lived, because increased synthesis of the mediator is combined with an increase in the synthesis of enzymes that inactivate it. (NA inactivates MAO, OAT).

Vagoergia - an increase in the excitability of the parasympathetic department. A lot of ACX, a lot of cholinesterase.

Amphoergia - an increase in the excitability of both parts of the autonomic nervous system.

Peripheral syndromes present best on the surface of the body and are associated with damage to sympathetic nerve fibers and include:

Syndrome of loss of sympathetic innervation:

• a) cessation of sweating dry skin;
• b) loss of the pilomotor reflex;
• c) during the first 10 days - hyperemia as a result of paralytic arterial hyperemia, later cyanosis appears as a result of spasm of arterioles and a decrease in blood flow.

Irritability Syndrome:

• a) hyperhidrosis as a result of activation of sweat glands;
• b) increased pilomotor reflex;
• c) changes in the skin - thickening, peeling of the skin, the formation of "ribbed", "claw-like" nails;
• d) sympathy;
• e) the formation of ulcers in the area that is involved in the irritation syndrome.

Syndrome of denervation hypersensitivity.

• a) vascular spasm. Mechanism: increased sensitivity of denervation tissue (its recipes) to humoral stimuli;
• b) increased sensitivity. Mechanism: increase in the number of ligand-free receptors, increase in the total number of receptors.

Trophy. Dystrophy.

Trophy - a set of processes that provide:

maintenance of cell metabolism;

maintaining the structural and morphological organization of the cell;

ensuring optimal cell activity.

This set of processes includes:

the entry of nutrients and gases into the cell,

utilization of incoming substances by the cell,

balancing the processes of assimilation and dissimilation,

synthesis of macromolecules and plastic material,

removal of metabolic products from the cell.

The normal trophic state of the cell is eutrophy.

Types of trophic disorders:

Quantitative: - hypertrophy;

• - malnutrition;
• - atrophy.

Qualitative: - dystrophy.

Dystrophy is a violation of trophism, which is accompanied by a violation of cell metabolism; violation of the properties of cell formations (membranes); violation of the properties of mitochondria. Changes in the cell genome and antigenic properties of the cell.

The overall result is a violation of the cell's ability to self-renewal and self-maintenance.

Trophic regulation mechanisms:

Humoral, including endocrine.

These are intercellular interactions.

Nervous control - carried out according to the reflex principle and the afferent and efferent nerves take part.

Neural control mechanisms:

Metabolic effects of mediators, they are most demonstrative in the implementation of continuous tonic impulsation, which contributes to the quantum release of mediators. Phasic impulsation = discrete, associated with a specific reaction of effectors. Mediators in small amounts can stimulate cell metabolism without reaching the severity of the effect of the organ.

Vascular - a change in the blood supply to an organ.

Increased permeability of histohematic barriers.

Afferent nerves carry out trophic influences in the zone of innervation through the antidromic current of the axoplasm, i.e. axoplasm moves towards the receptor.

Endocrine control - influence on metabolism.

Dystrophies caused by diseases of the nervous system - neurogenic dystrophies.

There are 4 groups of neurogenic dystrophies, according to

with the nature of the damage:

damage to afferent fibers.

damage to efferent fibers.

Damage to adrenergic fibers.

Damage to the nerve centers - centrogenic dystrophies.

Features of centrogenic dystrophies:

Rapid development of degeneration of afferent fibers.

Preservation of efferent influences.

Change of adrenergic influences.

Change in the release of neurohormones.

Pathogenesis of centrogenic dystrophies:

Termination of afferent impulses to the centers, tissue anesthesia.

Increased impulses to the nerve centers as a result of irritation of the proximal end of the damaged nerve.

Increased traumatization of the denervated organ.

Unusual impulsation along efferent fibers.

Changes in the a/g properties of tissues with the inclusion of autoimmune processes.

Unusual effector sensitivity.

Manifestations of centrogenous dystrophies:

dedifferentiation of tissues, death of combial elements (loss of ability to regenerate);

early cell death;

the formation of ulcers;

immune and autoimmune tissue damage and leukocyte infiltration.

(From the textbook of P.F. Litvitsky)

Distinguish protopathic and epicritical pain (pain sensitivity).

epicritical (“quick”, “first”, “warning”) pain occurs as a result of exposure to stimuli of low and medium strength. The properties of epicritical pain are shown in the table.

Comparativecharacteristicepicriticalandprotopathicpain.

property of pain	epicritic pain	protopathic pain
Source of irritant	skin, mucous membranes	internal organs and tissues
latent period	short	long
Duration after removal of the stimulus	stops quickly	long lasting
Type of conductive fiber	myelinated, type A	unmyelinated, type C
Threshold of perception	short	high
Localization	accurate	diffuse

Note. Characteristics of different types of nerve fibers are given in the article “Nerve fiber” in the appendix “Reference book”.

protopathic (“slow”, “painful”, “ancient”) pain occurs under the influence of strong, “destructive”, “large-scale” stimuli. Properties of protopathic pain are given in Table.

Only combined - both protopathic and epicritical - sensitivity makes it possible to subtly assess the localization of the impact, its nature and strength.

(Textbook by P.F. Litvitsky)
Pain classifications.

Currently, several classifications of pain have been proposed. Depending on the location of the damage, pain can be divided into somatic superficial (in case of damage to the skin), somatic deep (in case of damage to the musculoskeletal system), visceral (in case of damage to internal organs). Pain that occurs when peripheral nerves are damaged is called neuropathic pain, and when CNS structures are damaged, they are called central pain. If the pain does not coincide with the injury site, projected and reflected pain are distinguished. For example, when the spinal roots are compressed, the pain is projected into the areas of the body innervated by them. Referred pain occurs due to damage to internal organs and is localized in distant superficial areas of the body. So, in relation to the skin surface, pain is reflected on the corresponding dermatome, for example, in the form of Zakharyin-Ged zones.

In the clinic, to focus on the causes of pain, an etiological classification is used. Examples of such pain are: postoperative pain, cancer pain, arthritis pain, etc.

Of particular importance for the differentiated therapy of pain syndromes is the pathogenetic classification based on the identification of the main, leading mechanism in the formation of pathological pain. According to this classification, there are three main types of pain syndromes:

1. 
   somatogenic (nociceptive);
2. 
   neurogenic;
3. 
   psychogenic.

Pain syndromes arising from the activation of nociceptors during trauma, inflammation, ischemia, tissue stretching are referred to as somatogenic pain syndromes.

In turn, somatogenic pain is divided into:

somatic and visceral. Clinically, among them are: post-traumatic and postoperative pain syndromes, pain with inflammation of the joints, myofascial pain syndromes, vascular pain, pain in cancer patients, angina pectoris, pain in cholelithiasis and many others.

Development neurogenic pain syndromes are associated with damage to the peripheral or central structures of the nociceptive system and the formation of persistent aggregates of hyperactive neurons in them.

Examples of such pain syndromes are trigeminal neuralgia, phantom pain syndrome, thalamic pain, causalgia.

A special group is psychogenic pain or pain of a psychological nature, which can occur regardless of somatic, visceral or neuronal damage and is largely determined by psychological and social factors.

One of the mechanisms for the formation of this type of pain is the reflex muscle tension caused by psycho-emotional factors, which leads to the development of tissue ischemia and painful discomfort in the area of ​​tension. The most common example is tension headache. In anxiety-phobic states, pain can be seen as a conversion process that turns psychological conflict into physical suffering, which is maintained or intensified by negative memories and thoughts. In addition, psychogenic pain may occur as a delusion or hallucination in patients with psychosis and disappear when the underlying disease is treated.

By temporal parameters, allocate acute and chronic pain.

Acute pain is new, recent pain that is inextricably linked to the injury that caused it, and is usually a symptom of some disease. Such pain disappears when the damage is repaired.
Chronic pain often acquires the status of an independent disease, continues for a long period of time even after the cause of acute pain has been eliminated.

In some cases, the cause of chronic pain may not be determined at all. The pathogenesis of chronic pain syndrome is complex and is associated with the formation of a special pathodynamic state - a pathological algic system, which is the basis of stereotypical pain behavior. In this case, it must be remembered that pain is, first of all, an unpleasant sensation, accompanied by emotional stress. As defined by the Term Ordering Committee IASP, the activity that occurs in nociceptors and nociceptive pathways in response to noxious stimuli is not pain, but reflects the process of signal detection and transmission. The final assessment (perception) of nociceptive signals by our consciousness in the form of sensations, emotions and reactions depends on many psychological and social factors. Pain is always subjective. The same irritation can be perceived by our consciousness in different ways. Self-doubt, fear increase pain, while anger and rage reduce pain sensitivity. The perception of pain depends not only on the location and nature of the injury, but also on the conditions or circumstances under which the injury occurred, on the psychological state of the person, his individual life experience and culture. Thanks to the process of recognition, comparison of current pain with previous pain experience, the final manifestation of pain is largely determined - the severity of facial expressions, the presence or absence of groans, the degree of suffering, which are fixed in a special memory through memory mechanisms. “painful behavior" characteristic of patients suffering from chronic pain syndrome. It should be emphasized that chronic pain syndromes are characterized by a combination of pathogenetic mechanisms, when a psychogenic one, which aggravates the clinical manifestations of pain, is added to the leading main mechanism (somatogenic or neurogenic). Therefore, in the treatment of chronic pain syndromes, along with etiopathogenetic therapy, a well-thought-out correction of personality-psychological problems using psychotherapeutic methods (hypnosis, auto-training, group or family psychotherapy) is necessary.
Age and gender differences in pain perception

When diagnosing and treating a number of pain syndromes, it is necessary to take into account the peculiarities of pain perception in people of different sexes and different ages. This is especially important in the presence of pain syndromes of visceral origin. Clinical observations in most cases indicate that the intensity of pain perception decreases with age.

Men and women perceive and endure pain differently. It is known from surgical practice that girls and women in the first days of the postoperative period often complain of pain than boys and men. During dental procedures, it was also noted that women experience more intense pain than men. When presented with the same intensity of pain stimuli in women, the objective indicator of pain (dilation of the pupil) is more pronounced. A special study conducted on newborns showed that girls show a more pronounced facial reaction in response to pain irritation than boys. It is believed that the peculiarities of pain perception in men and women are due to hormonal differences between the sexes. In some pain conditions in women, differences in the perception of pain depending on maturation, pregnancy, menopause and aging have been described. In men, some pain pathologies also show a different character in different periods of life. In addition, in women, various forms of pain change depending on the phase of the menstrual cycle. Progesterone is associated with analgesia and anesthesia because some pain conditions (migraine) are relieved or relieved during pregnancy or in the mid-luteal phase of the menstrual cycle, and other types of pain are relieved in animals during lactation (when progesterone levels are elevated). Estrogen may enhance wound healing and may also induce analgesia, as some pain conditions increase after menopause when estrogen is reduced (eg, joint and vaginal pain). Similar considerations apply to testosterone because some pain symptoms, such as angina, become more pronounced in men as testosterone declines with age.

Animal experiments have shown that sex hormones, in particular estrogen and progesterone, affect the opiate system involved in the mechanisms of antinociception.

The number of children and adolescents suffering from chronic pain syndromes of various origins can reach 10-12% of the entire population. Girls experience chronic pain more often than boys, and the highest incidence of chronic pain in girls occurs at 12-14 years of age. Regardless of gender, several chronic pain syndromes may be present at the same time.

In patients older than 65 years, the number of painless heart attacks and painless gastric ulcers increases. However, this does not indicate a decrease in pain perception. In the elderly, the plasticity of the central nervous system is reduced, manifested by delayed recovery and an increase in the duration of pain after tissue damage.

Men and women perceive pain differently. In girls and women, the thresholds of pain perception and pain tolerance are lower than in boys and men. Women are more likely than men to experience headaches and visceral pain, both acute and chronic, during their lifetime. Visceral pain in certain pathologies of the internal organs is less predictable in women than in men, as a result of which these pathologies are less diagnosed and treated in women. Therefore, in the intraoperative and postoperative periods, women need more pain relief than men.
Pathophysiology of pain

Now, having some ideas about pain, it is important to understand the differences between acute (physiological) and chronic pain and realize that pathological (chronic) pain is not a symptom of a disease, but an independent pathological process, or a disease.

Physiological pain.

In the development of ideas about the perception of pain by the human body, there are 3 main stages (three main theories):

• 
  "specificity" theory
• 
  gate control theory
• 
  neuromatrix theory

More

First stage.

By the middle of the 20th century, a " specificity theory"According to which, pain is a separate sensory system in which any damaging stimulus activates special pain receptors (nociceptors) that transmit pain impulses along special nerve pathways to the spinal cord and pain centers of the brain, causing a protective response aimed at moving away from stimulus (see previous chapter). The psychological sensation of pain, its perception and experience are recognized as adequate and proportional to physical trauma and peripheral damage. In practice, this provision led to the fact that patients suffering from pain and not having obvious signs of organic pathology began to be considered "hypochondriacs", "neurotic" and, at best, were referred for treatment to a psychiatrist or psychotherapist.

Second phase.

Many researchers understood the imperfection of the theory of specificity, which assigned the role of a passive receiver of pain impulses to the central nervous system. In parallel with the theory of specificity, several variants of the "theory of patterns" were proposed, based on the concept of the summation of nerve stimuli up to a certain threshold, beyond which a pain sensation occurs.

In the 60s of the 20th century, the theory " gate control":

1. The transmission of nerve impulses to the central nervous system is modulated by special "gateway" mechanisms located in the posterior horns of the spinal cord.

2. Spinal "gateway" mechanisms, in turn, are regulated by descending impulses from the brain.

3. When a critical level is reached, the flow of impulses from spinal cord neurons activates the "System of Action" - neuronal zones of the central nervous system that form complex behavioral responses to pain.

The theory of "gate control" was of great practical importance. Methods of cutting nerves began to be replaced by methods of influencing the information entering the spinal cord. Physiotherapists, reflexologists and therapeutic gymnastics specialists use many modulating techniques, including acupuncture and transcutaneous electrical nerve stimulation (TENS in the treatment of acute and chronic pain.

This theory recognizes the spinal cord and brain as active systems that filter, select, and act on sensory inputs. The theory approved the central nervous system as the leading link in pain processes.

Third stage

Over time, facts appeared that were inexplicable from the standpoint of the “gate control” theory. Monitoring patients with paraplegia, i.e. with a break in the spinal cord, and patients suffering from phantom pain, retaining the experience and sensation of already missing parts of the body led to the following conclusions:

firstly, since the phantom limb is felt so real, it follows that its normal sensation is due to processes in the brain itself, which means that it can also occur in the absence of input proprioceptive signals;

secondly, since all sensory sensations, including pain, can also occur in the absence of stimuli, it can be considered that the sources of the emergence of neural patterns that form the quality of experience are not in the peripheral nervous system, but in the neuronal networks of the brain.

Consequently, the perception of one's own body and its diverse sensations is determined by the central processes in the brain, is genetically determined and can only be modified under the influence of peripheral signals and past experience.

This conclusion became the basis of the theory that approved a new conceptual model of the nervous system, the theory neuromatrix.

The neuromatrix is ​​an extensive network of neurons that form functional loops between the thalamus and the cortex, the cortex and the limbic system. The synaptic connections in this neural network are genetically determined and, in a sense, constitute the maternal "matrix" that generates, reproduces, and modulates sensory information.

However, although the neuromatrix is ​​predetermined by genetic factors, its synaptic individual architecture is formed and determined by the sensory signals and influences that enter it during a person's life. The neuromatrix is ​​an inseparable unity of heredity, experience and learning.

The neuromatrix theory states that all qualitative characteristics of pain sensation are genetically determined and generated in the brain, and peripheral stimuli are only their nonspecific "triggers".

According to the new concept, the brain not only perceives, analyzes and modulates input sensory signals. It has the ability to generate pain perception even in cases where no external impulses and irritations come from the periphery.

The neuromatrix theory is likely to be of significant clinical value in the treatment of persistent, particularly phantom pain. So, for example, the introduction of a local anesthetic (lidocaine) into certain areas of the brain (lateral hypothalamus, dentate nucleus, etc.), which is done quite easily and safely, can block the formation of pain neurosignatures for a period much longer than the duration of the pharmacological action. drug

Antinociceptive system

The complex of the nociceptive system is equally balanced in the body by the complex of the antinociceptive system, which provides control over the activity of the structures involved in the perception, conduction and analysis of pain signals.

It has now been established that pain signals coming from the periphery stimulate the activity of various parts of the central nervous system (periaductal gray matter, raphe nuclei of the brainstem, nuclei of the reticular formation, nucleus of the thalamus, internal capsule, cerebellum, interneurons of the posterior horns of the spinal cord, etc. ) exerting a downward inhibitory effect on the transmission of nociceptive afferentation in the dorsal horns of the spinal cord.

In the mechanisms of the development of analgesia, the greatest importance is attached to the serotonergic, noradrenergic, GABAergic and opioidergic systems of the brain.

The main of them, the opioidergic system, is formed by neurons, the body and processes of which contain opioid peptides (beta-endorphin, met-enkephalin, leu-enkephalin, dynorphin).

By binding to certain groups of specific opioid receptors (mu-, delta- and kappa-opioid receptors), 90% of which are located in the dorsal horns of the spinal cord, they promote the release of various chemicals (gamma-aminobutyric acid) that inhibit the transmission of pain impulses.

This natural, natural pain-relieving system is just as important to normal functioning as the pain-signaling system. Thanks to her, minor injuries such as a bruised finger or a sprain cause severe pain only for a short time - from a few minutes to several hours, without making us suffer for days and weeks, which would happen in conditions of persisting pain until complete healing.

Thus, physiological nociception involves four main processes:

1. Transduction - a process in which the damaging effect is transformed in the form of electrical activity in free non-encapsulated nerve endings (nociceptors). Their activation occurs either due to direct mechanical or thermal stimuli, or under the influence of endogenous tissue and plasma algogens formed during trauma or inflammation (histamine, serotonin, prostaglandins, prostacyclins, cytokines, K + and H + ions, bradykinin).

2. Transmission - the conduction of impulses that have arisen along the system of sensory nerve fibers and pathways to the central nervous system (thin myelin A-delta and thin non-myelin C-afferents in the axons of the spinal ganglia and posterior spinal roots, spinothalamic, spinomesencephalic and spinoreticular pathways coming from neurons dorsal horns of the spinal cord to the formations of the thalamus and limbic-reticular complex, thalamocortical pathways to the somatosensory and frontal areas of the cerebral cortex).

3. Modulation - the process of changing nociceptive information by descending, antinociceptive influences of the central nervous system, the target of which is mainly the neurons of the posterior horns of the spinal cord (opioidergic and monoamine neurochemical antinociceptive systems and the gate control system).

4. Perception - a subjective emotional sensation perceived as pain and formed under the influence of background genetically determined properties of the central nervous system and situationally changing stimuli from the periphery. (I quote from the author