Pathological algic system: antinociceptive system
Last reviewed: 23.04.2024
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Accumulated facts are combined in a harmonious theory of generator systems GN Kryzhanovskii (1980, 1997). The basis of pathological pain is the occurrence in the central nervous system of a generator of pathologically enhanced excitation (GPOO). The pathologically enhanced excitation generator is an aggregate of hyperactive neurons, producing an excessive uncontrolled flow of impulses. The GPOO is formed in the damaged nervous system from the primary and secondary altered neurons and represents a new pathological integration unusual for the activity of the normal nervous system that arises at the level of inter-neuronal relations. A feature of the generator is its ability to develop self-sustaining activity. The GPU can be formed practically in all departments of the central nervous system, its formation and activity are related to typical pathological processes.
The emergence of the generator serves as an endogenous mechanism for the development of the pathological process in the nervous system and nervous disorders. The GPOO is formed under the influence of various pathogenic factors of both exogenous and endogenous origin: this process has a polyethological nature. The generator's operation and the nature of the impulse flow produced by it are determined by its structural and functional organization. In the experiment, the pain syndromes are modeled by the creation of the GPU (application or injection of proconvulsant) in various parts of the nervous system: pain syndrome of spinal origin (a generator in the dorsal horns of the spinal cord), trigeminal neuralgia (a generator in the caudal nucleus of the trigeminal nerve), thalamic pain syndrome thalamus).
The hyperactivation (disinhibition) of neurons and the emergence of a generator is possible by synaptic and non-synaptic mechanisms. Long-existing generator, firstly, fixes its structure by neuroplastic changes, and, secondly, it has a pathological effect on other structures of the nociceptive system, integrating them into the pathological algic system (PAS). Clinically, the roar syndrome occurs when the somatic sensory and orbitofrontal cortex is included in the pathological algic system. An indispensable condition for the formation of the GURV and PAS is the weakness of the rhythmic systems, that is, the antinociceptive system (ANCS).
The basic organization of the pathological algic system: the levels and the formation of an altered pain sensitivity system that make up the main trunk of the PAS.
Peripheral departments: Sensitized nociceptors, foci of ectopic excitation (damaged and regenerating wounds, demyelinated nerve sites, neuromas); group of hyperstiminal neurons of spinal ganglia.
Spinal level: Units of hyperactive neurons (generators) in afferent nociceptive receptors in the dorsal horns and nuclei of the spinal tract of the trigeminal nerve (caudal nucleus).
Supraspinal level: The nucleus of the reticular formation of the trunk, the nucleus of the thalamus, the sensorimotor and the orbitofrontal cortex, the emotionogenic structures.
So, the task of the nociceptive system is to inform about the damaging effects. However, excessive, prolonged nociceptive impulses can cause disintegration of CNS activity and further numerous impairments and organic changes in other organs and systems.
Protection from excessive nociceptive information is provided by the system of analgesic defense - antinociceptive system (reciprocal regulation of functions). Activation of the antinociceptive system is carried out by a nociceptive stimulus. This is a particular example of the physiological phenomenon of the duality of the exciting premise. The same signal goes in two directions:
- on the nociceptive pathway, providing a perception of pain,
- to structures of analgesic defense, activating them to suppress nociceptive information.
In addition, the antinociceptive system is involved in suppressing insignificant nociceptive stimuli that do not pose a threat to the body. The weakness of the antinociceptive system can lead to a person beginning to sense these nociceptive signals, experiencing constant pain, as, for example, in fibromyalgia. At the same time, clinical and instrumental examination does not reveal a somatic or neural pathology capable of explaining chronic pain. This explains the effect of neurotropic drugs (enhancing the inhibitory functions of the CNS, activating the antinociceptive system in fibromyalgia.) The weakness of the antinociceptive system can lead to chronic pain in the clinically obvious pathology of the somatic sphere or the nervous system.
At the present time, it is shown that in the provision of analgesia (the work of the antinociceptive system), the posterior columns of the spinal cord, the core of the central gray matter, the paragen cell and giant cell nucleus of the reticular formation, the blue spot, the parabrachial nucleus, the black substance, the red and caudate nucleus, the nucleus of the septal region , tires, hypothalamus, tonsils, specific and nonspecific nuclei of the thalamus, frontal, motor and somatosensory cortex of the cerebral hemispheres, cerebellum. Between these structures there are close bilateral ties. Activation of the above structures suppresses the activity of nociceptive neurons at various levels of the central nervous system, with the greatest inhibitory effect on the neurons of the horn of the spinal cord.
In antinociception, the greatest importance is attached to opioidergic, monoaminergic (serotonin, noradrenaline) systems. Drugs that activate these mediator systems can be used in the treatment of acute and chronic pain (serotonin reuptake inhibitors and norepinephrine, opioids). The opioid system begins to control nociception beginning with the terminals of A-sigma and C-afferents, on which opiate receptors are found. Endogenous opioids are endorphins and enkephalins, which exert a morphine-like effect on these receptors. Actively involved in the mechanisms of regulation of pain sensitivity is also the GABA-ergic system. A significant role is played by endogenous cannabinoids (anandamide and arachidonate of glycerol).
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