Nervous System Disorders – Etiology, Causes, Pathogenesis, Conditions


Causes and conditions for the occurrence of disorders of the nervous system

In pathology of nervous system disorders, Pathogenic factors causing damage to the nervous system are exogenous or endogenous in nature. Exogenous pathogenic factors can be neurotropic, affecting certain structures of the nervous system, i.e. specific. Non-specificetiological factors damage not only the nervous, but also other tissues. Exogenous factors affecting the nervous system include biological pathogens: viruses (rabies, poliomyelitis), microbes (leprosy), plant toxins (strychnine, curare), microbial toxins (botulinum, tetanus), alcohols (ethyl, methyl), pesticides (chlorophos ), toxic substances, etc. The word is a specific pathogenic factor for a person. It can cause disorders of mental activity, behavior, disorders of various functions according to the conditioned reflex mechanism.

In pathology of nervous system disorders, Endogenous pathogenic factors are divided into primary and secondary. The primary ones are hereditary disorders of the activity of the genetic and chromosomal apparatus of neurons. They are associated with hereditary diseases of the nervous system (Down’s disease, endogenous psychoses, etc.), circulatory disorders in various parts of the central nervous system, ischemia, etc.

Secondary endogenous pathogenic effects include damage to internal organs and systems, when the nervous tissue is involved in the pathological process during the development of the underlying disease (hepatic encephalopathy, uremic coma, diabetic neuropathies and comas, etc.).

Etiological factors cause changes in the nervous system. The latter play the role of pathogenetic factors: changes in neurons, impaired release and reception of neurotransmitters, acquired alterations of the neuronal genome, changes in interneuronal relationships, nervous trophism, the formation of antibodies to nervous tissue, disruption of the work of antisystems (analgesic, anticonvulsant, etc.). Typical pathogenetic changes can be the formation of aggregates of hyperactive neurons, which are generators of pathologically enhanced excitation (GPVE), the formation of pathological determinants, pathological systems and pathological dominants.

Understanding of the features of pathogenesis and knowledge of the mechanisms of development of the pathological process are necessary for an adequate pathogenetic therapy. So, it is useless to treat tetanus toxin-induced lesions of the central nervous system only with tetanus toxin, which neutralizes tetanus toxin, since the latter has already associated with nerve elements and caused corresponding changes in the central nervous system (in particular, damage to proteins involved in the release of inhibitory transmitters). Therapy at this stage should be aimed at eliminating the effects of tetanus toxin (suppression of neuronal hyperactivity, fighting seizures, etc.). The use of anti-tetanus serum at this stage is necessary to neutralize new portions of tetanus toxin produced in the wound by tetanus bacillus.

The realization of pathogenic effects depends on their strength and duration – the stronger and longer these effects, the more significant their effect. However, even weak pathogenic effects, if they are prolonged and constant, can cause profound and lasting changes in the nervous system. For example, with fractional, repeated administration of neurotropic toxins (tetanus, botulinum, etc.), their total dose causing a pathological effect and death of the animal may be less than that which causes a similar effect with a single administration of the entire dose of toxin (Bering’s phenomenon). Daily electrical stimulation of brain structures by a current of subthreshold force, not accompanied by a visible reaction, causes an increase in the convulsive readiness of the brain. With the passage of time, the animal responds to the same subthreshold effects with convulsions (the phenomenon of “swinging”, or kindling). In everyday life

many stressful, neurozogenic factors, occupational hazards, etc. act for a long time.

Factors that do not cause pathology of the initially normal nervous system can acquire pathogenic significance for the nervous system, altered by previous pathological processes, with a genetically determined predisposition, increased excitability, etc. Limbic structures, in particular the hippocampus, are more capable of developing and maintaining pathological hyperactivity than others, which can be caused even by a single pathogenic effect.

In pathology of nervous system disorders, An important role in the preservation of pathological effects is played by the plasticity of the nervous system – the ability to consolidate the changes that have arisen. This property provides the possibility of its development, the formation of new connections, learning, structural changes, etc. However, plasticity is a blind force, it fixes not only biologically useful, but also pathological changes. Due to plasticity, the resulting structural and functional pathological changes in the nervous system (for example, synaptic disturbances, generated excitation generators, pathological systems, etc.) are fixed. In many cases, the chronicity of the pathological process and its resistance to therapeutic influences are associated with plasticity.

Pathogenetic changes in the nervous system are two kinds of phenomena. The first of them is damage and destruction of morphological structures, functional connections and physiological systems. It is designated I.P. Pavlov as “sex” and is the result of the direct action of a pathogenic agent. Another phenomenon is the emergence of new, pathological integrations from altered neural structures.

The “sex” itself is not a development of a pathological process. It plays the role of the cause and condition of this development, which is carried out by the own endogenous mechanisms of the damaged nervous system.

At the level of interneuronal relations, such integration is an aggregate of hyperactive neurons, at the level of intercellular relations – a new organization consisting of altered parts of the central nervous system – a pathological system. Thus, the actual pathogenesis of nervous disorders is characterized not only by destruction, but also by the emergence of pathological formations – an aggregate of neurons and a pathological system, i.e. happens once

destruction of physiological and the formation of pathological systems.

The entry of pathogenic agents into the nervous system (PATHOLOGY OF NERVOUS SYSTEM)

In pathology of nervous system disorders, There are two main routes of entry of pathogenic agents into the central nervous system – from the blood (through the vascular wall) and along the nerve trunks.

In the first case, the pathogenic agent (toxic substance, viruses, microbes, etc.) must overcome the blood-brain barrier (BBB), which is formed by the vascular wall (endothelial cells), as well as glial elements (astrocytes). The BBB carries out active and selective transport from the blood to the brain of nutrients and other biologically active substances necessary for brain activity. At the same time, it protects the brain from the direct action of pathogenic agents in the blood. In fetuses and newborns, the BBB is more passable. A number of toxic agents (strychnine, alcohols, some pharmacological drugs) pass the BBB relatively well. For biological pathogens (viruses, microbes), the BBB is normally impenetrable. However, in conditions of pathology, under the action of a number of physical and chemical factors, the BBB permeability increases, which complicates the pathological process. For example, severe prolonged stress promotes the entry of the influenza virus into the brain.

Nerve trunks are the routes of entry of a number of pathogenic agents into the central nervous system. The neural pathway is typical for tetanus toxin, poliomyelitis viruses, rabies, etc. The entrance gate for tetanus toxin is the myoneural synapse, from where the toxin enters the spinal cord and medulla oblongata through motor fibers. In the central nervous system, toxins (tetanus), viruses, antibodies to the nervous tissue can spread from neuron to neuron inside the nerve processes (with axotoc) and along the interneuronal spaces.

Nervous system defense mechanisms

In the pathology of nervous system disorders, The protective function of various membranes of the brain and nerves should also be added to the tissue barrier mechanisms. The protection of the neuron and its processes is provided by the surrounding glial and Schwann cells, as well as the membrane of the neuron itself. The nervous system is also protected by an immunological barrier.

A protective role is played by special regulatory “balancing” (according to IP Pavlov) mechanisms aimed at preventing and eliminating the resulting changes. In conditions of pathology, this principle is implemented in the activity of antisystems (G.N. Kryzhanovsky). The antisystem is activated or formed together with the formation of a pathological system, limiting the development of the latter and suppressing its activity. For example, when excessive pain occurs, the antinociceptive system is activated, which regulates pain sensitivity. Activation of the antinociceptive system stops the onset of pain.

The antiepileptic system controls the level of arousal in various parts of the central nervous system. Electrical stimulation of the caudal nucleus of the pons, which belongs to the antiepileptic system, suppresses activity in the epileptic focus in the cerebral cortex.

The tonic activity of the antisystem is one of the mechanisms for maintaining a stable state of health. Insufficient activity of antisystems is a condition for the development of a pathological process. For example, insufficiency of the antinociceptive system leads to the appearance of increased pain sensitivity and the formation of pain syndromes; failure of the antiepileptic system causes a predisposition to seizures.

Loss of functions of the nervous system (PATHOLOGY OF NERVOUS SYSTEM)

In the pathology of nervous system disorders, The loss of one or another function of the nervous system can be caused either by the destruction or inhibition of the activity of the structures performing this function. An example of a loss of function due to damage (destruction) of a structure can be flaccid muscle paralysis when the motor neurons of the spinal cord innervating it, affected by the polio virus, or when the motor nerve is interrupted or degenerated, can be. When structures related to sensory systems are damaged, the corresponding types of sensitivity (pain, visual, etc.) drop out.

The degree of loss of function is determined not only by the number of affected nerve cells. Around the lesion

a zone of reversibly damaged and inhibited neurons appears in the brain tissue. Inhibition plays the role of a protective mechanism (“protective inhibition” according to I.P. Pavlov), protecting neurons, reversibly damaged, from a functional load that may contribute to their death. In connection with the exclusion of these neurons from the performance of the function, the degree of the functional defect increases; such a situation occurs in poliomyelitis, trauma to the central nervous system, etc. Recovery in a particular volume of function under therapeutic influences is associated not with the regeneration of neurons (neurons do not regenerate), but with an improvement in the condition and normalization of the activity of reversibly damaged neurons and with the removal of protective inhibition.

Loss of function in the event of structural defects does not appear immediately. It occurs when the damage has reached such a size that the mechanisms of compensation and overlapping of the impaired function have already become insufficient. In other words, at this stage, the pathological process has reached significant development, and does not begin, as is commonly thought. In such cases, the doctor deals with an already rather advanced disease. That is why therapy is not always effective even at this, early stage, and the diagnosis of pathological changes at the preclinical stage of the process is so important .

Loss of function, due to inhibition of the activity of the structures of the central nervous system, can also occur with an increase in the inhibitory effect. So, if the parts of the medulla oblongata are hyperactive, which normally have an inhibitory effect on the reflexes of the spinal cord, then the function associated with spinal reflexes drops out. Reflex loss of sensitivity, hysterical paralysis, suggestive (self-hypnosis, or hypnotic) disturbances of movements and sensitivity, and other phenomena of inhibitory suppression of function are known.

Outcomes of pathological processes in the nervous system

In the pathology of nervous system disorders, The pathological process that has begun in the nervous system under conditions of continuing pathogenic influence can progress if sanitizing mechanisms are overcome. This will result in either hyperactivation or destruction and death of neurons. If the process covers the vital parts of the central nervous system, then the death of the organism occurs.

On the contrary, with the activation and development of sanitizing mechanisms, the pathological process is eliminated, the impaired functions are restored, clinical improvement occurs first, and then recovery.

If sanogenetic mechanisms are sufficient only to limit the pathological process and arrest its development, in particular, if they do not eliminate pathological systems, but only limit their development, then the process may stop. In these conditions, the pathological process becomes chronic. It is facilitated by ongoing pathogenic influences. They cause new damage, support pathological systems and disrupt sanitation mechanisms. Chronization of the pathological process is associated with the strengthening and stabilization of pathological systems.

In the later stages, when functions are restored to the required extent and the clinical signs of the pathological process completely disappear, hidden structural and functional changes in the form of traces from the former pathological process may persist.

The phenomenon of restoration of signs of a disappeared pathological process on the basis of trace reactions with a new pathogenic effect was called the phenomenon of “second impact”(A.D.Speransky). In an experiment using the “second blow” method, the possibility of reproduction of neuro-dystrophic ulcers after their disappearance, convulsive syndrome after clinical elimination of tetanus, various tissue and metabolic changes was shown. After the symptoms of neurosis caused by the flood disappeared in the dog (Leningrad, 1924), the deliberate launch of water on the floor of the cabin caused the animal to relapse of neurosis. With nervous and mental diseases, relapses of clinically disappeared signs of neuropathological syndromes often occur due to secondary pathogenic effects. Similar phenomena occur in diseases of the nervous regulation of the functions of internal organs (see section 21.8).

Secondary pathogenic agent, if it is non-specific, i.e. not the same one that was the cause of the given disease cannot cause the entire disease on the basis of trace reactions. Under the action of similar agents, individual symptoms of the former pathology may occur.


Inhibition deficit. Release

In the pathology of nervous system disorders, At rest and in an active state, neurons experience constant inhibitory influences. When neurons are excited, inhibitory processes are weakened. Such disinhibition is dosed, it is controlled and corresponds to the required level of neuron activity, therefore, it has a physiological character.

With pathological disinhibition, the neuron becomes overactive and out of control. Pathological disinhibition occurs when there is a significant and uncontrolled inhibition deficit. This condition occurs in conditions of direct damage to the inhibitory mechanisms, with the selective action of certain toxins (for example, tetanus toxin, strychnine) on them.

Deficiency of inhibition and disinhibition are found in almost all forms of pathology of the nervous system, therefore they

refer to typical pathological processes of the nervous system. The inhibition deficit plays an essential role in the formation and activity of the GPUV.

Decerebral rigidity is a characteristic experimental disinhibition syndrome It is caused, according to Sherrington, by cutting the brainstem between the anterior and posterior quadruples. Under these conditions, the suppression of inhibitory influences from the supraspinal structures and especially the red nuclei occurs, and the excitatory tonic effects of the vestibular nuclei of Deiters on the motor neurons of the spinal cord, especially γ-motor neurons, which are normally under inhibitory control from the red nuclei, appear. A break (for example, by cutting the posterior roots) of the disinhibited, pathologically enhanced γ-loop at the level of the spinal cord leads to the disappearance of the rigidity of the corresponding muscles. Therefore, this type of decerebration rigidity is also called γ-rigidity (R. Granite).

With the loss of inhibitory influences, primarily those neurons that are normally in a state of tonic excitation are disinhibited and hyperactivated. In humans and many animals, these neurons are muscle neurons that perform an antigravitational function. As a result, in a decerebrated cat, the head is thrown back up, the front and hind legs are extended, the tail is raised, etc. In humans, with the loss of motor cortical influences (for example, after a hemorrhagic stroke), a spastic flexor position of the upper limb and an extensor position of the lower limbs appear (Wernicke-Mann pose).

In the pathology of nervous system disorders, A number of pathological reflexes arise in conditions of loss of influences from the cortex and subcortical formations; these reflexes are the result of disinhibition of the centers of the spinal cord or medulla oblongata. They are hyperbolized uncontrolled reactions that were normal in the early postnatal period and then were suppressed with the development of regulatory influences from the higher parts of the central nervous system. These include the Babinsky reflex (spreading the toes apart instead of bending them when the sole is irritated), grasping, sucking and other reflexes.

With a complete interruption of the spinal cord, genetically inherent and suppressed with age spinal auto

tomatisms in the form of relatively coordinated flexion-extension movements of the limbs. If inhibitory neurons are disinhibited and hyperactivated, then a pathologically enhanced inhibitory effect arises, which can manifest itself in the form of suppression and loss of function.

Denervation syndrome (PATHOLOGY OF NERVOUS SYSTEM)

In the pathology of nervous system disorders, denervation syndrome is a complex of changes that occur in postsynaptic neurons, organs and tissues after the loss of nerve influences on these structures. The denervated structure (muscle, neuron) acquires an increased sensitivity to physiologically active substances (Kennon-Rosenbluth law). The main manifestation of the denervation syndrome in the muscle is the disappearance of the end plate – the zone of the muscle fiber, where its entire cholinergic apparatus is concentrated. Instead, new acetylcholine receptors appear throughout the muscle fiber, and in this regard, an increase in the overall sensitivity to acetylcholine of the entire fiber occurs (A.G. Ginetsinsky, N.M. Ashmarina). This effect is mainly associated with the loss of trophic influences of the nerve. Another characteristic feature is fibrillar twitching of the denervated muscle. This effect reflects the reaction of denervated muscle fibers to acetylcholine coming to them from various external sources.

With denervation, properties inherent in early, in particular, embryonic stages of development appear in muscle and other tissues. This phenomenon arises as a result of pathological disinhibition of genes that are normally suppressed.


In the pathology of nervous system disorders, An impulse entering a neuron, from whatever source it may come from, is afferent for the neuron. Turning off this afferentation is a deafferentation of the neuron. The latter can be caused either by the loss of incoming impulses (with a break in the nerve pathways, violation of the release of neurotransmitters by presynaptic endings), or a blockade of receptive receptors on the postsynaptic neuron (under the action of toxins, pharmacological agents, etc.).

Many phenomena during deafferentation of a neuron are an expression of denervation syndrome. Complete deafferentation of the neuron does not occur, since the neurons of the central nervous system have a huge number of afferent inputs. Nevertheless, even with partial deafferentation, an increase in the excitability of a neuron or its individual sections and a violation of inhibitory mechanisms occur. Due to this, during deafferentation, a group of neurons can acquire the properties of the GPUV.

In the clinic, the phenomenon of deafferentation refers to the syndromes that arise when afferent stimulation is lost from the periphery. These syndromes can be experimentally reproduced by transecting the corresponding dorsal roots of the spinal cord. The movements of the limb, innervated by the segments of the spinal cord deafferentiated in this way, become sweeping, poorly coordinated. In addition, such a limb is able to carry out spontaneous movements in time with breathing (the Orbeli-Kunstman phenomenon), which is caused by disinhibition and increased excitability of deaffected spinal cord neurons.

Spinal shock

In the pathology of nervous system disorders, Spinal shock occurs after a break in the spinal cord and is a deep but reversible suppression of motor and autonomic reflexes that occur below the break. The suppression of reflexes is associated with the loss of activating stimulation from the brain. In frogs, in which the dependence of the spinal cord on the brain is much less than in higher animals, spinal shock lasts several minutes, in apes and humans – several months.

In humans, complete areflexia after a break in the spinal cord is the initial stage of complete paraplegia. In the future, there is a gradual restoration of motor and autonomic reflexes. First, flexion reflexes of the fingers appear, which have the character of pathological reflexes (Babinsky’s reflex, etc.), after which more significant and then generalized spinal reflexes and movements such as spinal automatisms are carried out.

Violation of nervous trophism. Neurodystrophic process (PATHOLOGY OF NERVOUS SYSTEM)

Cell trophism and dystrophic process. Cell trophism is a complex of processes ensuring its vital activity and maintaining genetically inherent properties. Trophism disorder is a dystrophy, developing degenerative changes constitute a dystrophic process.

In the pathology of nervous system disorders, Neurodystrophic process. This is a developing violation of trophism, which is due to the loss or change in nervous influences. It can occur both in peripheral tissues and in the nervous system itself. The loss of nerve influences is: 1) in the termination of stimulation of the innervated structure in connection with a violation of the release or action of the neurotransmitter; 2) in violation of the secretion or action of comedians – substances that are secreted together with neurotransmitters and play the role of neuromodulators that ensure the regulation of receptor, membrane and metabolic processes; 3) in violation of the release and action of trophogens. Trophogens (trophins) are substances of various, predominantly proteinaceous nature, realizing the actual trophic effects of maintaining vital activity and genetically inherent properties of the cell. The source of trophogens are: 1) neurons, from which trophogens come with anterograde (orthograde) axoplasmic current into recipient cells (other neurons or innervated tissues in the periphery); 2) cells of peripheral tissues, from which trophogens come along nerves with retrograde axoplasmic current into neurons; 3) glial and Schwann cells, which exchange trophic substances with neurons and their processes. Substances that play the role of trophogens are also formed from serum and immune proteins. Certain hormones can have a trophic effect. Peptides, gangliosides, and some neurotransmitters are involved in the regulation of trophic processes. from which trophogens enter neurons via nerves with retrograde axoplasmic current; 3) glial and Schwann cells, which exchange trophic substances with neurons and their processes. Substances that play the role of trophogens are also formed from serum and immune proteins. Certain hormones can have a trophic effect. Peptides, gangliosides, and some neurotransmitters are involved in the regulation of trophic processes. from which trophogens enter neurons via nerves with retrograde axoplasmic current; 3) glial and Schwann cells, which exchange trophic substances with neurons and their processes. Substances that play the role of trophogens are also formed from serum and immune proteins. Certain hormones can have a trophic effect. Peptides, gangliosides, and some neurotransmitters are involved in the regulation of trophic processes.

By normotrofogenam include various kinds of proteins that promote growth, differentiation and survival of neurons and somatic cells preserve their structural homeostasis (e.g., nerve growth factor).

Under conditions of pathology, trophic substances are produced in the nervous system, causing persistent pathological

Trophic connections of the motor neuron and muscles. Substances from the body of a motor neuron (MN), its membrane 1, perikaryon 2, nuclei 3 are transported with anterograde axoplasmic current 4 to terminal 5. From here they, as well as substances synthesized in terminal 6 itself, enter transsynaptically through the synaptic cleft (SC) into the terminal plate (CP) and into muscle fiber (MV). Part of the unused material comes back from the terminal to the body of the neuron with retrograde axoplasmic current 7. Substances formed in the muscle fiber and the end plate enter transsynaptically in the opposite direction to the terminal and then with a retrograde axoplasmic current 7 into the body of the neuron – to the nucleus 8, into the perikaryon 9, to the membrane of dendrites 10. Some of these substances can flow from dendrites (D) transynaptically to another neuron through its presynaptic ending (PO) and from this neuron further to other neurons. Between the neuron and the muscle, there is a constant exchange of substances that support trophism, structural integrity and normal activity of both formations. Glial cells take part in this exchange (D). All these formations create a regional trophic system (or trophic contour) changes in recipient cells (pathotrophogens, according to G.N. Kryzhanovsky). Such substances are synthesized, for example, in epileptic neurons – entering other neurons with axoplasmic current, they can induce epileptic properties in these recipient neurons. Pathotrophogens can spread along the nervous system, as in the trophic web, which is one of the mechanisms of the spread of the pathological process. Pathotrophogens are formed in other tissues as well.

In the pathology of nervous system disorders, Dystrophic process in a denervated muscle. Substances synthesized in the body of a neuron and transported to the terminal with an axoplasmic current are released by the nerve ending and enter the muscle fibers, performing the function of trophogens. The effects of neurotrophogens can be seen from experiments with severing the motor nerve: the higher the transection is made, i.e. the more trophogens are preserved in the peripheral segment of the nerve, the later the denervation syndrome sets in. The neuron together with the structure innervated by it (for example, muscle fiber) forms a regional trophic contour, or regional trophic system. If we carry out cross-reinnervation of muscles with different initial structural and functional characteristics (reinnervation of “slow” muscles with fibers from neurons that innervated “fast” muscles, and vice versa),

In the denervated muscle fiber, new trophogens arise, which activate the proliferation of nerve fibers (sprouting). These phenomena disappear after reinnervation.

In the pathology of nervous system disorders, Neurodystrophic process in other tissues. Mutual trophic influences exist between each tissue and its nervous apparatus. When the afferent nerves are cut, dystrophic changes in the skin occur. The transection of the sciatic nerve, which is mixed (sensory and motor), causes the formation of a dystrophic ulcer in the hock joint. Over time, the ulcer can grow in size and cover the entire foot.

The classic experiment of F. Magendie (1824), which served as the beginning of the development of the entire problem of nervous trophism, consists in cutting the first branch of the trigeminal nerve in a rabbit.

Those such operations develop ulcerative keratitis, inflammation occurs around the ulcer, and from the side of the limbus, vessels grow into the cornea, which are normally absent in it. Vascular ingrowth is an expression of pathological disinhibition of vascular elements – in the dystrophically altered cornea, a factor that normally inhibits the growth of vessels in it disappears, and a factor appears that activates this growth.

Additional factors of the neurodystrophic process. The factors involved in the development of the neurodystrophic process include: vascular changes in tissues, disorders of hemo- and lymphomicrocirculation, pathological permeability of the vascular wall, impaired transport of nutrients and plastic substances into the cell. An important pathogenetic link is the emergence of new antigens in dystrophic tissue as a result of changes in the genetic apparatus and protein synthesis, antibodies to tissue antigens are formed, and autoimmune and inflammatory processes occur. This complex of pathological processes also includes secondary infection of the ulcer, the development of infectious lesions and inflammation. In general, neurodystrophic tissue lesions have a complex multifactorial pathogenesis (N.N. Zaiko).

Generalized neurodystrophic process. With damage to the nervous system, generalized forms of the neurodystrophic process can occur. One of them manifests itself in the form of lesions of the gums (ulcers, aphthous stomatitis), tooth loss, hemorrhage in the lungs, erosion of the mucous membrane and hemorrhage in the stomach (more often in the pylorus), in the intestine, especially in

In the pathology of nervous system disorders, the area of ​​the boisin’s valve, in the rectum. Since such changes occur relatively regularly and can occur with various chronic nerve damage, they are called the standard form of nervous dystrophy (A.D.Speransky). Often these changes occur when the higher vegetative centers are damaged, in particular, the hypothalamus (with injuries, tumors), in the experiment when a glass ball is applied to the Turkish saddle.

All nerves (motor, sensory, autonomic), whatever function they perform, are at the same time trophic (A.D.Speransky). Disturbances of nervous trophism constitute an important pathogenetic link in diseases of the nervous system and nervous regulation of somatic organs; therefore, correction of trophic changes is a necessary part of complex pathogenetic therapy.



Violation of arousal

In the pathology of nervous system disorders, The propagation of excitation along the nerve fiber is ensured by a sequential combination of the same processes: depolarization of a portion of the fiber membrane, entry of Na + in this portion, depolarization of an adjacent portion of the membrane, entry of Na + in this portion, etc.

If the Na + input is insufficient, the generation of the action potential is disturbed, and the conduction stops. This effect takes place in the blockade of Na + -channels with local anesthetics (novocaine, lidocaine, etc.) and a number of other chemical agents. A specific blocker of Na + -channels is tetrodotoxin, a poison produced in the internal organs of puffer fish.

The initial difference in the concentration of Na + and Ka + on both sides of the membrane (Na + is 10-15 times more outside, K + is 50-70 times more inside), which is necessary to generate an action potential, is restored and maintained by the active transport of Na + / K + -pump ions. It pumps out the Na + that has entered (into the cytoplasm) during arousal, in exchange for external K +, which has come out during arousal. The activity of the pump, the role of which is played by the Na + / K + – ATPase built into the membrane, is provided by the energy released during the

splitting of ATP. A lack of energy leads to a malfunction of the pump, which leads to the inability of the membrane to generate an action potential and conduct excitation. This effect is caused by uncouplers of oxidative phosphorylation (for example, dinitrophenol) and other metabolic poisons, as well as ischemia and prolonged cooling of the nerve site. They inhibit the pump and, as a consequence, disrupt the conductivity of cardiac glycosides (for example, ouabain, strophanthin) in large doses.

Conduction of excitation along the axon is disrupted in various types of pathology of peripheral nerves and nerve fibers in the central nervous system – in inflammatory processes, cicatricial changes in the nerve, compression of nerve fibers, fiber demyelination (allergic processes, multiple sclerosis), burns, etc. Conduction of excitation stops with axon degeneration.

Violation of axonal transport and dendrites

In the pathology of nervous system disorders, Axonal transport from the neuron body to the nerve ending and from the nerve ending to the neuron body is carried out with the participation of neurofilaments, microtubules, and contractile actin and myosin-like proteins, the contraction of which depends on the Ca 2 + content in the medium and on the energy of ATP cleavage. Substances that destroy microtubules and neurofilaments (colchicine, vinblastine, etc.), a lack of ATP, metabolic poisons that create an energy deficit (dinitrophenol, cyanides) disrupt the axotoc. Axonal transport is affected by axon degeneration caused by a lack of vitamin B 6 and vitamin B 1(beriberi disease), industrial poisons (acrylamide, hexachlorophos), heavy metal salts (lead), pharmacological drugs (disulfiram), alcohol, diabetes, nerve compression and dystrophic neuron damage. When the axon is interrupted, Waller degeneration (decay) of its peripheral part and retrograde degeneration of the central part occur. These processes are associated with a violation of trophism in both parts of the axon.

Disorders of the axonal transport of trophogens and substances necessary for the formation and release of mediators by the nerve ending cause the development of dystrophic changes in neurons and innervated tissues and impairment of synaptic processes. The spread with axonal transport of pathotrophogens, antibodies to nervous tissue and to neurotransmitters leads

to the involvement of neurons in other parts of the central nervous system in the pathological process.

Dendrites and their spines are the most vulnerable structures of a neuron. With aging, the spines and branches of dendrites are reduced, with some degenerative and atrophic diseases of the brain (senile dementia, Alzheimer’s disease), they disappear. The dendroscopic apparatus suffers from hypoxia, ischemia, concussion, stress and neurotic effects.

Pathology of structural elements of neurons (PATHOLOGY OF NERVOUS SYSTEM)

In the pathology of nervous system disorders, Disturbances of intracellular structural homeostasis play a significant role in neuronal pathology. Normally, the processes of wear and decay of intracellular structures and neuronal membranes are balanced by the processes of their renewal and regeneration. The totality of these processes constitutes dynamic structural homeostasis.

Damage to both the cellular (cytoplasmic) and intracellular membranes occurs under various pathogenic influences and are themselves the cause of further pathology of the neuron.

Enhanced lipid peroxidation (LPO) of neuronal membranes affects not only membrane, but also other intracellular processes.

There is practically no pathological process in the nervous system, in which increased LPO would not occur. It occurs in epilepsy, endogenous psychoses (for example, schizophrenia, manic-depressive syndrome), with neuroses, stress and damage, with ischemia, chronic hypoxia, functional neuronal overload, etc. Further overactive neurons are associated with it.

Due to the increase in membrane permeability, various substances exit the neuron, including antigens, which cause the formation of anti-neuronal antibodies, which leads to the development of an autoimmune process. Violation of the barrier properties of membranes causes an increase in the current of Ca 2 + and Na + ions into the neuron and K + – from the neuron; these processes in combination with the insufficiency of energy-dependent Na + -, K + – and Ca 2 + -pumps (their activity also changes under the influence of enhanced lipid peroxidation) lead to partial depolarization of the membrane. Increased inlet Ca 2 + not

only causes hyperactivation of the neuron, but even with its excessive content in the cell, it leads to pathological changes in metabolism and intracellular damage (see Chapter 3).

Normalization of lipid peroxidation and stabilization of neuronal membranes should be part of a comprehensive pathogenetic therapy for various forms of pathology of the nervous system.

For the vital activity of a neuron, which, as a highly differentiated cell, is not capable of mitotically dividing, intracellular regeneration is the only way to structurally renew neurons and maintain their integrity. This includes the synthesis of proteins, the formation of intracellular organelles, mitochondria, membrane structures, receptors, the growth of nerve processes (axons, dendrites, dendritic spines), etc.

Intracellular regeneration processes require high energy and trophic supply and full cell metabolism. When a neuron is damaged, an energy and trophic deficit occurs, and the activity of the genome is disrupted, intracellular regeneration suffers, the plastic potential of the cell decreases, and the disintegration of intracellular structures is not balanced by them.


The need for energy supply of neurons is the highest of all cells in the body, and impaired energy supply is one of the most common causes of neuron pathology. Energy deficit can be primary – under the action of metabolic poisons (for example, dinitrophenol, cyanides) or secondary – with various injuries, circulatory disorders, shock, edema, general convulsions, increased functional load, etc. Energy deficiency belongs to the category of typical intracellular pathological processes ( see chapter 3).

In the pathology of nervous system disorders, The main conditions for the development of energy deficiency are a lack of oxygen and significant damage to mitochondria, in which the main carrier of energy, ATP, is synthesized. Energy deficiency can also be caused by a lack of an oxidation substrate, in particular glucose, which is the main oxidation substrate for the brain. The neurons of the cortex do not have glucose reserves and consume it directly from the blood (glucose freely passes through the BBB), so they are especially sensitive

are susceptible to hypoglycemia. The brain consumes about 20% of all glucose in the blood. Insulin shocks used to treat some psychoses are associated with profound hypoglycemia and occur with loss of consciousness and often with convulsions. In a number of pathological conditions (traumatic shock, blood loss), the brain can be provided with oxygen and glucose for a longer time due to the redistribution of blood and a decrease in their consumption by other tissues. For the fastest recovery of brain activity after general seizures, a sufficiently high level of glucose in the blood is required. Energy deficiency is exacerbated by a violation of the Krebs cycle.

With a profound violation of oxidative phosphorylation and synthesis of macroergs, anaerobic glycolysis becomes the source of energy. It has the character of a compensatory mechanism, but its effect cannot compensate for the energy deficit, and the increasing increase in the content of lactic acid in the brain has a negative effect on the activity of neurons and aggravates cerebral edema.

The effects of ischemia and hypoxia

Due to the high demand for energy, the neurons of the central nervous system require significant oxygen supply. A neuron of the cerebral cortex consumes 250-450 μl of O 2 / min (for comparison, gliocyte and hepatocyte consume up to 60 μl of O 2 ). Reducing oxygen consumption by the brain by as little as 20% can cause loss of consciousness in a person. The disappearance of the impulse activity of neurons occurs already in the first tens of seconds of cerebral ischemia. In 5-6 minutes after the onset of asphyxia, a deep and often irreversible impairment of brain activity occurs. The death of a neuron during ischemia is the result of a complex of interconnected intracellular processes.

With anoxia of the brain, the cortex is the first to suffer. The death of the whole brain means “brain death”, which manifests itself in the complete disappearance of bioelectric activity. Phylogenetically older structures of the central nervous system (spinal cord, brain stem) are less sensitive to asphyxia than younger ones (subcortex and especially the cortex). Therefore, with a belated revival of the organism, decortication may occur.

Braking mechanisms are very sensitive to anoxia. One of the consequences of this is disinhibition of intact CNS structures. In the early stages of ischemia, when the brain’s neurons are still capable of reacting, they can become hyperactive. In the later stages of ischemia, the hyperactivation of neurons is replaced by their inactivation.

The entry of Na + into the neuron is associated with the first, acute phase of neuronal damage. An increase in the concentration of Na + in the cytosol of a neuron leads to an increase in osmolarity, which causes water to enter the neuron and its swelling. In the future, an increase in the osmolarity of the neuron is also associated with the accumulation of Ca 2 +, lactic acid, inorganic phosphorus in it. The second phase of neuron damage is associated with the Ca 2 + entry into the neuron . The increase in the amount of Ca 2 + entering the neuron is due to the activation of glutamate receptors due to the increased release of glutamate by nerve endings during ischemia. Antagonists of glutamate receptors and antagonists of Ca 2 + (blockers of Ca 2+ -channels) method-

we prevent ischemic degeneration of neurons and have a therapeutic effect.

Neuron damage occurs not only during ischemia, but also in connection with reperfusion of the brain and the resumption of blood circulation. They can be the main danger. An important role in post-ischemic reperfusion injuries is played by a new wave of Ca 2 + influx into the neuron, LPO (lipid peroxidation), and free radical oxidation processes, enhanced by the action of incoming oxygen. The content of lactic acid increases due to the intake of glucose under conditions of impaired oxidative phosphorylation and increased anaerobic glycolysis. Edema of the brain occurs due to the flow of water from the blood when circulation resumes.

The complex complex of Ca 2+ -induced intracellular damage includes: alteration of intracellular proteins, enhanced phospholipase hydrolysis and proteolysis, destruction of intracellular structures, damage to the cytoplasmic and intracellular membranes, swelling of neurons, disruption of genome activity. With a critical increase in the intensity of these processes, irreversible damage and death of the neuron occur, so-called calcium death occurs 1 .

At the later stages of the pathological process caused by cerebral ischemia, as well as during the chronicity of the process, a new complex of secondary changes arises – degenerative-dystrophic processes, disorders of enzyme and metabolic systems, vascular changes, the formation of antibodies to brain tissue, autoimmune aggression, etc. They constitute the pathogenetic structure postischemic encephalopathy, which may continue to develop (progressive development). These processes, as well as changes in other systems and organs with their consequences, also take place after the resuscitation of the body, especially if it was protracted and late. Together, they constitute the pathogenetic structure of postresuscitation disease (V.A.Negovsky) (see section 1.4.2).

1 Violation of Ca 2 + intracellular homeostasis can occur not only with ischemia, but also with other forms of pathology of the nervous system, with excessive and prolonged hyperactivation of the neuron, especially under conditions of energy deficit, with increased action of glutamate, etc. It belongs to typical intracellular pathological processes.

In the pathology of nervous system disorders, Hypoxia to one degree or another accompanies many (if not all) forms of brain pathology. Being a typical and non-specific process, it, however, can make a significant contribution to its development. At the same time, moderate hypoxia can stimulate metabolic and plastic processes in the neuron, promote adaptation and increase resistance, increase the trophic and plastic potential of the neuron, and enhance the adaptive capabilities of the brain.

Synaptic stimulation and neuronal damage (PATHOLOGY OF NERVOUS SYSTEM)

Excitatory synaptic stimulation may play an important role in the development of neuronal pathology. Enhanced and prolonged synaptic stimulation by itself causes a functional overstrain of the neuron, which can result in the degeneration of intracellular structures. These damages are enhanced by disorders of microcirculation and cerebral circulation, by the action of toxic factors.

Synaptic stimulation is of paramount importance in the development of anoxic (ischemic) damage. The tissue culture of neurons becomes sensitive to anoxia only after the establishment of synaptic contacts between neurons. Synaptic stimulation is realized through the action of excitatory amino acids (glutamate, aspartate, L-homocysteinate), and these damages are similar to those that occur during ischemia and are associated with an increased content of intracellular Ca 2+ . This effect is known as neurotoxic(or cytotoxic) action of excitatory amino acids. Damage and death of neurons in status epilepticus and in the postischemic period are associated with synaptic hyperactivation, the action of excitatory amino acids and hypoxia. In this case, an energy deficit is added to the pathogenic effect of these factors.

In connection with the above, the beneficial effects (ie weakening of the synaptic effect) of reducing the functional load, preventing additional stimuli, “protective”, according to I.P. Pavlov, inhibition of reversibly damaged neurons.

Disruption of neuron activity during changes in intracellular signaling processes

In the pathology of nervous system disorders, After the receptor perceives the signal (binding by the receptor of a neurotransmitter, hormone, etc.), a cascade of chain metabolic processes occurs in the neuron, providing the necessary activity of the neuron. An important role in these processes is played by the so-called amplifying, or triggering, enzymes and the intermediary substances formed under their influence, the secondary messengers (see Chapter 20).

The totality of cascade membrane and intracellular processes constitutes the endogenous amplifying system of a neuron, which can provide multiple amplification of the input signal and an increase in its effect at the output of the neuron. Thus, the cascade of metabolic processes of the adenylate cyclase pathway can enhance the effect of the stimulus by 10 7 -10 8 times. Thanks to this, it is possible to identify and implement a weak signal, which is of particular importance in conditions of pathology, with a violation of synaptic conduction.

Many changes in neuron functions are associated with the action of pathogenic agents on certain links of intracellular signaling systems. Pharmacological correction of neuron activity and the effects of therapeutic agents are also realized through appropriate changes in these systems. So, cholera and pertussis toxins act on processes associated with the activity of membrane G-proteins that activate or inhibit adenylate cyclase. Xanthines (theophylline, caffeine) cause the accumulation of cAMP, which leads to increased neuron activity. Under the action of a number of anticonvulsants (for example, diphenylhydantoin, carbamazepine, benzodiazepines) and psychotropic drugs (for example, triftazine), different pathways of protein phosphorylation are inhibited, thereby reducing the activity of neurons. Lithium ions, used in the treatment of certain endogenous psychoses, weaken the activity of the phosphoinositide system. With enhanced Ca input2 + epileptization related neurons of the input block antagonists Ca 2 + suppresses seizure activity.

Neuron hyperactivity (PATHOLOGY OF NERVOUS SYSTEM)

The hyperactivity of the neuron is caused by a significant, out of control imbalance between arousal and

inhibition of the neuron in favor of excitation. In functional terms, it consists in the production of an increased flow of impulses by the neuron, which can have a different character: high-frequency action potentials; separate categories; discharges grouped into packs, etc. A special type of hyperactivity is a paroxysmal depolarization shift (PDS) in the membrane, at the height of which a high-frequency discharge occurs. This type of hyperactivity is considered as a manifestation of neuron epileptization.

This shift in the balance between excitation and inhibition can be caused either by primary increased excitation of the neuron, overcoming inhibitory control, or by primary insufficiency of inhibitory control. The first mechanism is realized by a significant depolarization of the membrane and an increased entrance of Na + and Ca 2 + into the neuron, the second – by a disorder of the mechanisms that ensure membrane hyperpolarization: a violation of the exit of K + from the neuron and the entrance of Cl  into the neuron.

An essential endogenous regulator of neuronal activity is γ-aminobutyric acid (GABA). It causes inhibition of a neuron when it binds to its receptor. As a result, the influx of Cl  into the neuron is enhanced .

When a neuron is disinhibited, due to weakening of inhibition and membrane depolarization, an increase in the supply of Ca 2 + to the neuron occurs . In addition, Ca 2 +, being already in the cytosol, disrupts the entry of C1  into the neuron, thus weakening GABAergic inhibition from within. This is associated with epileptization of the neuron, which occurs under the influence of convulsants, which disrupt GABAergic inhibition. Many convulsants (for example, penicillin, corazole, etc.) have a complex effect on the neuron, simultaneously activating excitatory and inactivating inhibitory mechanisms.

Chronic stimulation of a neuron (for example, with direct electrical stimulation, synaptic exposure, under the influence of excitatory amino acids, etc.), even at low intensity, can lead to hyperactivation of the neuron over time. On the other hand, turning off the afferentation of a neuron also causes its hyperactivation. This effect is explained by an increase in the sensitivity of the neuron and a violation of inhibitory processes.

Thus, pathological hyperactivation of neurons, their epileptization is a complex complex of various membrane and intracellular processes. To suppress epileptic activity, it is advisable to use complex substances that normalize the main pathogenetic links of the process. Among the corrective actions, the blockade of Ca 2 + intake and the restoration of brake control are of paramount importance .



Concept and general characteristics

In the pathology of nervous system disorders, Disorder of the central nervous system occurs when exposed to a sufficiently powerful stream of impulses that can overcome the mechanisms of regulation and inhibitory control of other parts of the central nervous system and cause their pathological activity. Such a powerful stream of impulses is produced by a group of hyperactive neurons that form a generator of pathologically enhanced excitation (G.N. Kryzhanovsky).

The HPUV is an aggregate of hyperactive interacting neurons that produce an uncontrolled flow of impulses. The intensity and nature of this flow do not correspond to the incoming signal and are determined only by the features of the structural and functional organization of the generator. Due to the fact that the generator’s neurons activate each other, the generator is able to self-sustain its activity, without the need for constant additional stimulation from the outside.

Arising when the nervous system is damaged, the generator becomes a pathogenetic factor in the development of the process. Its formation has the character of a universal mechanism and is a typical pathological process that occurs at the level of interneuronal relations. The electrophysiological expression of the generator’s activity is the total potentials of its constituent neurons. An example of such potentials is the electrical activity recorded in the generator region in the giant cell nucleus of the medulla oblongata and in the epileptic focus in the cerebral cortex, which is one of the types of generator.

Pathogenetic significance of GPVV. The main pathogenetic significance of the generator lies in the fact that it hyperactivates the part of the central nervous system in which it originated or with which it is directly connected, as a result of which this department acquires the value of a pathological determinant (see Section 21.5), which forms the pathological system (see Sec. 21.6). Since pathological systems underlie the corresponding nervous disorders (neuropathological syndromes), the formation of a generator is the initial link in these disorders.

Formation and activity of generators of pathologically enhanced excitation

The generator can be formed under the action of various substances of an exogenous or endogenous nature, causing either a violation of the mechanisms of inhibitory control (which entails disinhibition and hyperactivation of neurons), or direct hyperactivation of neurons. In the latter case, the inhibitory mechanisms are preserved, but they are functionally ineffective and unable to normalize the activity of neurons. In all cases, a prerequisite for the education and activity of the generator is the lack of inhibition of its constituent neurons.

An example of the formation of a generator in a primary disorder of inhibition can be generators arising from the action of tetanus toxin, strychnine, penicillin and other convulsants. An example of generator formation during primary hyperactivation

neurons can be generators arising from enhanced and prolonged synaptic stimulation, the action of excitatory amino acids (in particular, glutamate), shallow ischemia and postischemic reperfusion of the central nervous system. The generator can also occur during deafferentation of neurons after transection of nerves and spinal cord, which is associated with deafferentation pain syndromes.

In the early stages of generator development, when the inhibitory mechanisms are still preserved, and the excitability of neurons is low, the generator is activated by sufficiently strong stimuli entering through a certain input into the group of neurons that comprise it. In the later stages, when there is a deep failure of the inhibitory mechanisms and the excitability of neurons is significantly increased, the generator can be activated by various stimuli from different sources, as well as spontaneously.



Concept and general characteristics

In the pathology of nervous system disorders, The formation of a generator does not always lead to the occurrence of pathological reactions. When the propagation of the generated excitation is blocked by the mechanisms of inhibitory control, the generator is functionally isolated and does not cause systemic pathological effects. Pathology arises if the central nervous system, hyperactivated under the influence of the generator, actively influences other formations of the central nervous system, involves them in a pathological reaction and unites them into a new organization – the pathological system (G.N. Kryzhanovsky). In many cases, in particular in the early stages of the formation of a pathological system and in acute cases, such a hyperactive part of the central nervous system determines the nature of the activity of the pathological system, it acquires the value of a pathological determinant.Any formation of the central nervous system (department, nucleus, nerve center, etc.) can play the role of a pathological determinant.

Pathogenetic significance of the pathological determinant. The pathological determinant is the formative, key and governing link of the pathological system. The emergence of a determinant belongs to the category of typical pathological processes that occur at the systemic level.

An example of a pathological determinant in the cerebral cortex is a powerful epileptic focus, under the influence of which a complex of disparate, weaker foci of epileptic activity is formed. Such a focus forms an epileptic complex, which is a pathological (epileptic) system. If you suppress using pharmacological agents or surgically remove a determinant focus, then com-

the plex disintegrates and instead of it separate epileptic foci reappear.

The emergence and activity of a pathological determinant

In the pathology of nervous system disorders, The determinant can unite the structures of the central nervous system into a pathological system and determine the nature of the activity of these structures. If the regulation of structures that perceive impulses from neurons of the determinant is weakened, then the determinant subordinates them to its influences.

In the early stages of the development of nervous disorders, the pathological determinant is activated by specific stimuli, i.e. stimuli that are adequate for the formation of the central nervous system, which has become a determinant (for example, light stimuli, if the determinant is formations in the system of the visual analyzer, painful – if the determinant has arisen in the system of pain sensitivity, etc.). This pattern also extends to disorders of higher nervous activity, neurotic reactions: their determinant is easily activated by the action of those stimuli that caused its formation (for example, the same conflict neurotic situations, etc.). These features determine the specificity of the provoking influences that cause seizures in nervous disorders.

In the later stages, the determinant can be activated by stimuli of a different nature, and therefore seizures can be provoked by different influences. In addition, the pathological determinant can be activated accidentally due to the spontaneous activation of the generator.

Parts of the central nervous system experiencing a long-term influence of a pathological determinant may become determinants themselves over time. Initially, such a secondary determinant is dependent on the primary one: it disappears if the primary determinant is eliminated. In the future, the secondary determinant may acquire an independent pathogenetic significance. Sometimes the secondary determinant turns out to be stronger than the primary one and becomes the leading one. Establishment of primary and secondary determinants is important for understanding the pathogenetic features of nervous disorders, their correct diagnosis and pathogenetic therapy.

The pathological determinant is the most resistant part of the pathological system. When the pathological system is suppressed or during its natural elimination, the determinant structure is preserved even when other formations of the system have already normalized and left its composition (“the determinant dies last”). When the pathological system is restored under the influence of new influences, the determinant structure is activated earlier than others (“the determinant resurrects first”).



Concept and general characteristics

In the pathology of nervous system disorders, The pathological system is a new pathodynamic organization that arises in the central nervous system under conditions of damage, the activity of which has a biologically negative significance (G.N. Kryzhanovsky). The main feature of a pathological system is its maladaptive or direct pathogenic significance for the body. This feature distinguishes the pathological system from the physiological one, the activity of which has an adaptive value and is aimed at achieving a result useful for the body.

In some cases, the pathological system arises as a result of hyperactivation and out of control of the physiological system, in others – by involving damaged and intact formations of the central nervous system into a new, previously non-existent structural and functional organization.

The emergence of the pathological system is the next stage in the development of the pathological process. The formation and activity of the pathological system belong to the category of typical pathological processes that are realized at the level of systemic relations.

A clear example of the activity of the pathological system is the pathological scratching reflex. It occurs when a generator is created in the brachial part of the spinal apparatus of the scratching reflex. The apparatus of the scratching reflex becomes a pathological determinant, which turns the physiological scratching reflex into a pathological one. The animal begins to comb the reflex projection zone with its hind paw. This scratching occurs spontaneously. Over time, as the pathological system develops, they become more and more

frequent, prolonged and violent, and may result in tissue tearing. The animal is not able to stop these scratching, despite their futility and harmful effect. This kind of indomitable violent behavior is observed in many forms of pathology of the nervous system in humans.

Structural and functional organization and features of the pathological system

The key control link is the pathological determinant with its mechanism of hyperactivation in the form of a generator (block G-D). Intermediate (block P) and central efferent links (block CE) develop activities that correspond to the characteristics of the activity of the pathological determinant. If the pathological system has access to the periphery, then its structure includes a peripheral organ, which becomes a target organ (OM block). In this case, the activity of the pathological system manifests itself in the form of an altered organ function – a pathological effect (PEF block). If the final link of the pathological system structures the brain, then its effect is expressed in the violation of the corresponding functions of the brain.

From all links of the pathological system there are negative feedbacks to the same links and to the determinant. However, unlike the physiological system, where such connections regulate the activity of the system, in the pathological system they are functionally ineffective, since they do not correct (or poorly correct) the pathological determinant, which, due to insufficient inhibitory mechanisms, gets out of control. The braking mechanisms are relatively insufficient in other parts of the pathological system. Therefore, the system as a whole is practically out of the general integrative control of the central nervous system. Along with this, due to constant activity, positive connections between parts of the pathological system are strengthened, the conduction of excitation through these connections is facilitated.

In the early stages of the process, the pathological system, following the pathological determinant, is activated by specific stimuli for it; in the later stages, it can be activated by various, including random, stimuli, as well as spontaneously. Therefore, in the later stages, seizures characteristic of the activity of this pathological system (for example, epileptic seizures, emotional affects, bouts of pain, etc.) can be provoked by various irritations, occur spontaneously, becoming more frequent, prolonged and intense.

At the initial stage, the pathological system is dependent on the pathological determinant, it is activated when the determinant is excited and disappears when it is eliminated. At later stages, due to the strengthening of the structure of the pathological system, the latter is less dependent on the determinant and can continue to act after its removal.

Pathogenetic significance of the pathological system (PATHOLOGY OF NERVOUS SYSTEM)

In the pathology of nervous system disorders, Pathological systems underlie a variety of nervous disorders related to various areas of the nervous system, therefore, their formation has the value of an almost universal pathogenetic factor.

The activity of the pathological system is clinically expressed in the form of a neuropathological syndrome or symptoms. Each syndrome has its own pathological system. Simple, linear pathological systems manifest as symptoms or monomorphic syndromes. An example of a relatively simple pathological system is the pathological system of the pathological scratching reflex described above. Multilevel, branched pathological systems serve as the pathogenetic basis of complex polymorphic syndromes. Parkinsonism, emotional-behavioral disorders, etc. can be cited as examples of such pathological systems.

The successively realized pathogenetic triad “generator – pathological determinant – pathological system” is the mechanism of occurrence of various nervous disorders.

This position underlies the reproduction of experimental models of various neuropathological syndromes: central pain of spinal origin (generator in the dorsal horns of the spinal cord); trigeminal neuralgia (generator in the caudal nucleus of the trigeminal nerve); thalamic pain syndrome (generator in the intralaminar nucleus of the thalamus); vestibulopathy – the rat rotates around the longitudinal axis of its body (generator in the vestibular nucleus of Deiters); photogenic epilepsy (generator in the visual analyzer system – in the lateral geniculate body); pathologically prolonged sleep (generator in the somnogenic system); a complex psychoaffective pathological state (generator in the emotiogenic system); pathological food-gathering behavior such as a violent form of behavior (generator in the lateral hypothalamus);

One of the important mechanisms of the functioning of the pathological system is that it suppresses the activity of physiological systems, including antisystems, and compensatory processes. This mechanism contributes to the development of the pathological process, especially with the continued action of the etiological factor.

Elimination and restoration of the pathological system

In the pathology of nervous system disorders, Unlike the physiological system, which after reaching the programmed biologically beneficial (adaptive)

the result is eliminated, the pathological system can operate indefinitely. This is due to the preservation of the pathological determinant and the consolidation of positive connections between parts of the pathological system. The elimination of the pathological system is due to the weakening of the influence of the pathological determinant and the activation of antisystems. It can occur naturally with the mobilization of sanogenetic mechanisms and with the action of therapeutic agents.

The elimination of the pathological system is carried out according to a single pattern – there is a consistent normalization of the activity of those parts of the system that experience the least influence from the pathological determinant. Therefore, the reduction of the pathological system is carried out due to the exit from it of the parts of the system least dependent on the pathological determinant. The pathological determinant persists longer than others. When it disappears, a local, weakened generator may remain, which does not cause significant pathological effects. Then the generator also disappears. When traces of the former pathological system are activated, the latter can be restored. So there is a relapse of nervous disorders, which are based on the pathological system.

Removal of the pathological system at the expense of the central efferent parts, with appropriate therapeutic effects, leads to the disappearance of clinical symptoms or syndromes, since under these conditions it cannot manifest itself as a violation of the functions of the target organ … However, at the same time, other parts of the pathological system remain and the threat of its restoration remains. Treatment aimed at normalizing only the efferent links and the target organ of the pathological system is not pathogenetic, but symptomatic.

At the same time, the specified reduction of the pathological system may be clinically effective. Removal of the pathological system leads to a decrease in the resistance of the rest of it due to a decrease in the number of positive connections that strengthen this system. Reducing the number of links in the system contributes to its destabilization and elimination. It is important that the disorganizing effect of the pathological system on other systems of the central nervous system decreases.

In the early stages, the elimination of the pathological determinant leads to the elimination of the pathological system. In the late centuries

diyah due to the formation of secondary pathological determinant or system can be restored, or to continue to exist after the elimination of the primary pathological determinants. The strengthening of the pathological system leads to the chronicity of the pathological process and the corresponding nervous disorders.

The fight against pathological systems, especially with complex and chronic forms, is very difficult and not always effective. It requires complex pathogenetic therapy aimed at eliminating the pathological determinant and normalizing other links of the pathological system, activating antisystems, enhancing general control and other sanogenetic mechanisms, and should be combined with etiological therapy to prevent the action of pathogenic factors that support pathological systems.


The concept and general characteristics of the dominant

In the pathology of nervous system disorders, The dominant, according to A.A. Ukhtomsky, is the currently dominant functional structure of the central nervous system – the center, the physiological system. The dominance of this structure over others is carried out through the conjugate inhibition of these structures. Dominant relationships are important for the activity of the nervous system: due to the inhibition of other systems, the physiological system currently operating is not interfered with. This ensures that the programmed result is achieved to the extent required, without distortion. Violations of dominant relationships can occur in various forms of pathology of the nervous system; they are a typical pathological process that occurs at the level of systemic relationships.

Types of violations of dominant relationships and their pathogenetic significance

In the pathology of nervous system disorders, Violation of dominant relationships is expressed either in the form of their insufficiency, or in the form of their excessive strengthening. And in fact, and in another case, pathology occurs.

In case of insufficiency of dominant relations, the activity of the currently active system is disrupted due to the influence of other systems on it. Under these conditions, the result of the activity of this system does not correspond to the one that should be achieved. With a profound violation of the dominant relationship, such a result cannot be achieved at all.

With an excessive strengthening of the dominant relationship, the pathology consists in the fact that the physiological systems and other structures of the central nervous system experience strong inhibition due to the activity of the dominant system. The hyperactive pathological system acquires the value of a pathological dominant – it causes oppression of physiological systems.

Normally, the physiological dominant and determinant are the working principles of the nervous system. The dominant, due to the inhibition of other systems, provides the possibility of normal activity of the currently active system, while the determinant determines the features of the activity of this system. The dominant is the mechanism of intersystem relations, the determinant is the mechanism of intrasystem relations.



Concept and general characteristics

In the pathology of nervous system disorders, Functional disorders arise not only as a result of damage to molecular and cellular processes, but also as a result of dysregulation of these processes. If dysregulation plays the main pathogenetic role, the emerging disorders have the character of dysregulatory pathology, or diseases of regulation. When nervous regulation suffers, diseases of nervous regulation arise (G.N. Kryzhanovsky).

In diseases of nervous regulation, the initial link in the development of the pathological process is changes in the regulatory apparatus or primary damage to the target organ. Pathologically altered regulation of organ activity is a factor that determines the development of secondary or further changes in the target organ.

Disturbances of nervous regulation can be caused by changes in both the central and peripheral links of the regulatory apparatus. The clinical expression of these

PS are related syndromes. In the event that internal organs serve as target organs, neurovisceral pathology occurs If autonomic centers become a pathological determinant, the resulting syndromes represent autonomic pathology.

Examples of diseases of nervous regulation. Diseases of nervous regulation constitute a wide class of various disorders. These include neurogenic forms of cardiac arrhythmias and hypertension, autonomic diencephalic paroxysms, neurogenic dyskinesias of internal cavity organs (stomach, intestines, gallbladder, fallopian tubes, uterus, etc.), some forms of gastric and duodenal ulcers, bronchial asthma, diabetes, , various kinds of vegetative crises, the so-called paroxysmal states, etc.

Those forms of pathology, which in everyday life are often referred to as “neuroses of internal organs” (for example, “cardiac neurosis”, “neurosis of the stomach”, etc.), are diseases of nervous regulation. They belong to neurotic disorders with certain pathological systems, the target organs of which are the corresponding visceral organs. The involvement of this or that formation in the structure of the pathological system depends on whether the mechanisms of regulation of this formation will be overcome by the influences of the determinant. The own mechanisms of regulation of the target organ are also important. So, under normal conditions with experimental cardiac arrhythmias caused by the creation of a generator in the central nervous system, heart rhythm disturbances begin to manifest themselves only with prolonged action of the generator.

Diseases of regulation, including diseases of nervous regulation, are usually referred by the doctor to the so-called functional pathology, saying that there are no organic changes. In the target organ, pronounced structural changes may appear at later stages of the process.

The principles of treatment of diseases of nervous regulation

Treatment aimed only at normalizing the altered function of an internal organ is not pathogenetic, but

symptomatic. Its results are usually short-lived, and relapse may occur if maintenance therapy is withdrawn. Pathogenetic treatment should consist in the elimination of the pathological system, in the normalization of the apparatus of nervous regulation. It is important to use complex pathogenetic therapy in the form of a combined effect on the regulatory apparatus, other parts of the pathological system and on the target organ. Etiological therapy should be to eliminate the factors that cause and maintain disorders of nervous regulation.



Concept and general characteristics

In the pathology of nervous system disorders, Pain is a complex psycho-emotional unpleasant sensation, which is realized by a special system of pain sensitivity and the higher parts of the brain. She signals

influences causing tissue damage, or pre-existing damage. The system of perception and transmission of the pain signal is also called the nociceptive system 1 .

Distinguish between physiological and pathological pain. Physiological pain is an adaptive defense mechanism. It signals the action of damaging agents, damage that has already occurred, and the development of pathological processes in tissues. Physiological pain activates protective processes and behavioral reactions aimed at eliminating the action of the painful (algogenic) factor and the consequences of this action.

People with congenital or acquired (for example, trauma, infectious lesions) pathology of the nociceptive system, deprived of pain sensitivity, do not notice damage, which can lead to serious consequences.

Pathological pain has maladaptive and pathogenic significance. Various types of pathological pain appear as characteristic syndromes and symptoms that are absent in physiological pain. These include causalgia, hyperpathy, primary and secondary hyperalgesia, expansion and appearance of new algogenic receptive zones, persistent pain, spontaneous attacks of pain, persistence of pain after

1 From lat. take – damage and earring – perceive. The corresponding terminology (nociceptive effects, nociceptors, etc.) was introduced by Sherrington. 

scheniya action of a provoking stimulus and other phenomena. Pathological pain is carried out by the same nociceptive system, but altered under pathological conditions.

Pathological pain causes the development of structural and functional changes and damage in internal organs, in particular in the cardiovascular system, tissue dystrophy, impaired autonomic reactions, changes in the activity of the nervous, endocrine and immune systems, psychoemotional sphere and behavior. Extreme pain can cause severe shock, uncontrollable chronic pain can cause disability. Pathological pain becomes a pathogenetic 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 difficult to combat. If pathological pain occurs a second time (with severe somatic diseases, malignant tumors, etc.),

Pathological pain of peripheral origin

In the pathology of nervous system disorders, This type of pathological pain occurs with chronic irritation of pain receptors (nociceptors), damage to nociceptive fibers, spinal ganglia and dorsal roots. These structures become a source of intense and often constant nociceptive stimulation. Nociceptors can be activated during chronic inflammatory processes (for example, with arthritis), the action of tissue breakdown products (for example, with tumors), etc. Chronically damaged (for example, when compressed by scars, overgrown bone tissue, etc.) and regenerating sensitive nerves, degeneratively altered (under the action of various hazards, 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 +, etc.).

A special role of such a source is played by a neuroma – the formation of chaotically grown nerve fibers, which occurs when they are disordered and difficult to grow. These endings

are sensitive to various mechanical, thermal, chemical and endogenous influences (for example, to catecholamines). Therefore, pain attacks with neuromas, as well as with nerve damage, can be triggered by various factors (for example, with emotional stress, the action of adrenaline).

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), consisting of the apparatus of inhibitory neurons of the gelatinous substance. These neurons regulate the flow of incoming and upward nociceptive stimulation into the posterior horns. This effect can take place with intense afferent stimulation or with insufficient inhibitory mechanisms of “gate control”.

Pathological pain of central origin

In the pathology of nervous system disorders, This type of pathological pain is associated with hyperactivation of nociceptive neurons at the spinal and supraspinal levels. Such neurons form aggregates, which are generators of pathologically enhanced excitation. With the formation of a generator in the posterior horns of the spinal cord, central pain syndrome of spinal origin occurs, with the formation in the nuclei of the trigeminal nerve – trigeminal neuralgia, in the nuclei of the thalamus – thalamic pain syndrome.

In the early stages of the pathological process, an attack of pain caused by the activation of the generator is provoked by nociceptive stimuli from a certain receptive field directly connected with the generator; in the later stages, an attack is provoked by stimuli of varying intensity 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 characteristics of the functioning of the generator and the pathological system. The nature of the pain itself (dull, acute, localized, diffuse, etc.) is determined by which formations of the nociceptive system have become parts of the pathological algic system.

A generator in the central apparatus of the nociceptive system can arise, for example, in the dorsal horns during prolonged nociceptive stimulation from the periphery. In these conditions, pain is the first

of initially peripheral origin, it acquires a central component and becomes a pain syndrome of spinal origin. This situation occurs with causalgia, neuromas and damage to the afferent nerves, with neuralgia, etc.

A generator in the central nociceptive apparatus can also occur during deafferentation, due to an increase in the sensitivity of deafferent nociceptive neurons and impaired inhibitory control. Deafferent pain syndromes can appear after amputation of limbs, transection of nerves and dorsal roots, after a break or transection of the spinal cord. In this case, the patient may feel pain in an insensitive or non-existent part of the body (for example, in a non-existent limb, in parts of the body below the transection of the spinal cord). This type of pathological pain is called phantom (from the word “fantom” – a ghost). It is caused by the activity of the central generator, the activity of which is no longer dependent on nociceptive stimulation from the periphery.

The generator in the central parts of the nociceptive system can occur in case of infectious damage to these parts (herpetic and syphilitic injuries), trauma, and toxic effects. In the experiment, such generators and the corresponding pain syndromes are reproduced by introducing into the corresponding sections of the nociceptive system substances that cause disturbance of inhibitory mechanisms (tetanus toxin, penicillin), or activate nociceptive neurons (potassium ions, etc.).

Secondary generators can form in the central apparatus of the nociceptive system. So, after the formation of a generator in the posterior horns of the spinal cord, after a certain time, a secondary generator can arise in the thalamus. Often, when the primary generator is localized in the spinal cord, in order to prevent impulses from entering the brain, a partial (interruption of the ascending tracts), and in severe cases even a complete cut of the spinal cord pathways, is performed.

Pathological algic system

Arising in the afferent input (dorsal horns of the spinal cord or the caudal nucleus of the trigeminal nerve), the generator itself is not capable of causing pathological pain. A local generator in the spinal cord can cause regional changes: facilitation of the flexor reflex, changes in the activity of motor neurons, etc.

Pathological pain as suffering and as a syndrome occurs if other parts of the pain sensitivity system are also involved in the process, in particular, the structures of the brain responsible for the manifestations of the feeling of pain, its emotional color.

The participation of these structures in the formation of pathological pain is not simply in their responses to incoming nociceptive signals, as in physiological pain. The section of the pain sensitivity system, in which the generator originated, becomes hyperactive and acquires the ability to change the functional state of neurons at other levels. From the primary and secondary altered formations of the pain sensitivity system, a new pathological integration is formed and fixed by plastic processes – the pathological algic system (PAS). That part of the pain sensitivity system, under the influence of which the pathological algic system is formed, plays the role of a determinant of PAS.

If the pathological algic system turns out to be unformed, if it does not include the higher parts of the pain sensitivity system – the thalamus and the cerebral cortex – the pain syndrome is not behaviorally manifested. This situation can occur if the nociceptive neurons in the dorsal horn are not active enough and do not form a generator, or if the higher parts of the pain sensitivity system have effective inhibitory control. In both cases, the role of a controlling mechanism that prevents the formation and activity of the pathological algic system is played by the antinociceptive system.

Table 21-1 shows the levels and formations of the pain sensitivity system included in the pathological algic system, which arises as a result of enhanced nociceptive stimulation from the periphery. These formations constitute the main trunk of the PAS, from them there are connections to various parts of the central nervous system, the involvement of which in the pathological process causes additional syndromes. The latter include autonomic disorders, changes in the cardiovascular system and microcirculation, dysregulation of the functions of internal organs, endocrine and immune systems, psychoemotional disorders, etc.

The course of the pain syndrome and the nature of pain attacks depend on the characteristics of the activation and activity of the PAS. An important role in this process is played by the features of the generator activation, with which

The activity of PAS is related to this. With a significant violation of the inhibitory mechanisms and increased excitability of neurons, their hypersynchronization occurs, and the generator is discharged by a rapidly increasing flow of impulses. If this flow causes an equally rapid and intensified activation of the pathological algic system, then the pain attack has a paroxysmal character. If the generator develops its activity slowly and the PAS is activated just as slowly, then the intensity of pain during an attack slowly increases; with tonic activity of the generator and PAS, the pain is constant.

Table 21-1. Levels and formations of the altered system of pain sensitivity, which constitute the main trunk of the pathological algic system

Peripheral divisions

Sensitized nociceptors, foci of ectopic excitation (damaged and regenerating nerves, demyelinated areas of nerves, neuroma); groups of hyperactivated neurons of the spinal ganglia

Spinal level

Aggregates of hyperactive neurons (generators) in afferent nociceptive relays – in the dorsal horns of the spinal cord and in the nuclei of the spinal tract of the trigeminal nerve (caudal nucleus)

Supraspinal level

The nuclei of the reticular formation of the trunk, the nucleus of the thalamus, the sensorimotor and orbitofrontal cortex, emotiogenic structures


Antinociceptive system (PATHOLOGY OF NERVOUS SYSTEM)

In the pathology of nervous system disorders, The nociceptive system has its own functional antipode – the antinociceptive system, which controls the activity of the structures of the nociceptive system.

The antinociceptive system consists of a variety of nerve formations belonging to different departments and levels of organization of the central nervous system, from the afferent input in the spinal cord to the cerebral cortex. Each relay switching in the nociceptive system has its own apparatus for monitoring the activity of its constituent nociceptive neurons. The nociceptive and antinociceptive systems make up the general system of pain

sensitivity, which determines the nature of nociceptive signaling, the measure of its perception and reaction to it.

The antinociceptive system plays an essential role in the mechanisms of prevention and elimination of pathological pain. By being involved in the reaction to nociceptive stimuli, it weakens the ascending stream of nociceptive stimulation and the intensity of the pain sensation, due to which the pain remains under control and does not acquire a pathological character. If the activity of the antinociceptive system is impaired, nociceptive irritations of even low intensity cause excessive pain. This effect takes place, for example, in congenital or acquired insufficiency of the antinociceptive mechanisms of the spinal cord, in particular, with insufficient “gate control”, with disturbances in the conduction of excitation through thick fibers that activate this control, with injuries, infectious lesions of the central nervous system, etc.

In cases of insufficiency of the antinociceptive system, its additional and special activation is necessary. The latter is carried out in various ways. Direct electrical stimulation of antinociceptive brain structures is effective, which can cause suppression of even severe pathological pain. Many analgesics, in particular opioids, exert their effect not only through a direct suppressive effect on nociceptive neurons and blockade of synaptic transmission of excitation, but also through the activation of structures of the antinociceptive system. By activating the antinociceptive system, non-drug pain suppressants (eg acupuncture) also act. Electrical stimulation of thick fibers, which activates “gate control” and other mechanisms of the antinociceptive system, is used in the clinic to suppress many types of pain,

At the same time, hyperactivation of the antinociceptive system can cause inadequate hypoalgesia and even deep suppression of pain sensitivity. Such effects arise during the formation of a generator in the structures of the antinociceptive system. Hysterical loss of pain sensitivity, analgesia that occurs during severe stress and some psychoses are also associated with increased activity of the antinociceptive system.


Neurochemical mechanisms of pain

In the pathology of nervous system disorders, Functional neurophysiological mechanisms of pain sensitivity system activity are implemented by neurochemical processes at various levels of the nociceptive and antinociceptive systems.

Peripheral nociceptors are activated under the influence of many endogenous biologically active substances – histamine, substance P, kinins, prostaglandins, etc. An important role in conducting excitation in primary nociceptive neurons

substance R. plays. It is considered as a mediator of pain. Capsaicin (a substance found in red pepper) causes a disruption in the synthesis of substance P; the introduction of capsaicin intrathecally into the spinal cord area causes prolonged analgesia; the action of capsaicin may be associated with the analgesic effect of the pepper patch. Substance P is also present in the higher levels of the nociceptive system, but excitation is carried out in them mainly by those neurotransmitters that are inherent in the neurons of these levels. Various neuropeptides are involved in the processes of excitation in different parts of the nociceptive system, which, like in other parts of the central nervous system, play the role of neuromodulators.

The neurochemical mechanisms of the antinociceptive system are realized by endogenous neuropeptides and classical neurotransmitters. Analgesia is usually induced by the combined or sequential action of several transmitters.

Opioid neuropeptides (enkephalins, endorphins) are effective endogenous analgesics. They have a depressing effect on transmitting neurons and activating – on neurons of the antinociceptive system, stimulate the system of diffuse nociceptive inhibitory control (DNTC), change the activity of neurons in the higher parts of the brain that perceive nociceptive stimulation and participate in the formation of pain. Their effects are also realized through the action of serotonin, norepinephrine and other neurotransmitters. Other neuropeptides (neurotensin, cholecystokinin, bombesin, angiotensin, vasopressin, etc.) also cause analgesia. Substance P can also induce analgesia and suppression of even pathological pain when it acts on antinociceptive structures, for example, on the dorsal suture nucleus.

Of the classical neurotransmitters, serotonin, norepinephrine, dopamine, and GABA play an important role in the implementation of analgesic effects. Serotonin is a mediator of the antinociceptive system at the spinal level. At the same time, one of the parts of the serotonergic system takes part in the activity of the nociceptive system, it expands the fields of nociceptive sensitivity.

Norepinephrine is also a mediator of the descending antinociceptive system, it suppresses the activity of nociceptive

nye neurons of the posterior horns of the spinal cord and nuclei of the trigeminal nerve. In addition, norepinephrine suppresses pain mechanisms at the supraspinal level. Its analgesic effect is associated with the activation of α-adrenergic receptors, as well as with the involvement of the serotonergic system. Therefore, the activator of central α-adrenergic receptors clonidine causes a pronounced analgesic effect.

GABA is involved in suppressing the activity of nociceptive neurons and pain at the spinal level. Disruption of GABAergic inhibitory processes (for example, by exposing the posterior horns to tetanus toxin, penicillin, etc.) causes the formation of a generator in them and severe pain syndrome of spinal origin. In the midbrain and medulla oblongata, GABA can inhibit the neurons of antinociceptive structures and weaken the mechanisms of pain relief at this level.


Principles for the treatment of pathological pain (PATHOLOGY OF NERVOUS SYSTEM)

In the pathology of nervous system disorders, The main principle of the treatment of pathological pain is to suppress the hyperactivity of nociceptive neurons and the generators they generate, and to eliminate the pathological algic system underlying the pain syndrome.

This goal is achieved by a combination of two influences: 1) the influence on the nonspecific, standard basic processes of neuronal hyperactivation, the formation and activity of the generator, which are fundamentally the same in different parts of the central nervous system; 2) influence on specific neurochemical processes, which are associated with the activity of nociceptive neurons, generators and various nociceptive pathological systems (pathological algic system).

Correction of the basic processes of neuronal hyperactivation and generator formation can be carried out with the help of anticonvulsants (antiepileptic drugs). Thus, a high therapeutic effect is provided by the use of the antiepileptic drug carbamazepine (tegretol, finlepsin) for the treatment of trigeminal neuralgia and other pain syndromes, especially of an acute paroxysmal nature. Suppress some pain syndromes and other anticonvulsants.

Of paramount importance for the suppression of the hyperactivity of nociceptive neurons is the blockade of Ca 2 + entry into them , which is carried out with the help of Ca 2 + antagonists.

Since nociceptive and antinociceptive effects are realized at different levels and, moreover, not by one, but by several mediators, it is advisable to use complex pathogenetic therapy in the form of a combined effect on different links of the pathological algic system in order to suppress it and the antinociceptive system in order to activate it. In addition, it is also important to influence the psychoemotional, vascular and other vegetative and tissue components of pathological pain. It is necessary to eliminate the action of the etiological factor that supports pathological changes in the nociceptive system.