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The pathologic algic system: the antinociceptive system
Last reviewed: 08.07.2025
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The accumulated facts are united into a coherent theory of generator systems by G.N.Kryzhanovsky (1980, 1997). The basis of pathological pain is the emergence of a generator of pathologically enhanced excitation (GEI) in the CNS. The generator of pathologically enhanced excitation is an aggregate of hyperactive neurons producing an excessive uncontrolled flow of impulses. GEI is formed in the damaged nervous system from primarily and secondarily altered neurons and represents a new pathological integration unusual for the activity of the normal nervous system, arising at the level of interneuronal relations. A feature of the generator is its ability to develop self-sustaining activity. GEI can be formed in almost all parts of the CNS, 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 GPPV is formed under the influence of various pathogenic factors of both exogenous and endogenous origin: this process has a polyetiological nature. The activity of the generator and the nature of the impulse flow produced by it are determined by its structural and functional organization. In the experiment, pain syndromes are modeled by creating the GPPV (application or injection of a proconvulsant) in various parts of the nervous system: pain syndrome 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 nuclei of the thalamus).
Hyperactivation (disinhibition) of neurons and the emergence of a generator are possible through synaptic and non-synaptic mechanisms. A long-existing generator, firstly, consolidates its structure with neuroplastic changes, and, secondly, has a pathological effect on other structures of the nociceptive system, involving them in the pathological algic system (PAS). Clinically, howling syndrome manifests itself when the somatosensory and orbitofrontal cortex are included in the pathological algic system. A prerequisite for the formation of GPUS and PAS is the weakness of the rhmotic systems, i.e. the antinociceptive system (ANCS).
The fundamental organization of the pathological algic system: levels and formations of the altered pain sensitivity system, which constitute the main trunk of the PAS.
Peripheral regions: Sensitized nociceptors, foci of ectopic excitation (damaged and regenerating wounds, demyelinated areas of nerves, neuromas); groups of hypersensitized neurons of the spinal ganglia.
Spinal level: Aggregates 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: Nuclei of the reticular formation of the brainstem, nuclei of the thalamus, sensorimotor and orbitofrontal cortex, emotiogenic structures.
Thus, the task of the nociceptive system is to inform about damaging effects. However, excessive, prolonged nociceptive impulses can cause disintegration of the CNS activity and then numerous dysfunctions and organic changes in other organs and systems.
Protection from excessive nociceptive information is provided by the pain protection system - the 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 duality of the excitatory message. The same signal goes in two directions:
- along the nociceptive pathway, providing the perception of pain,
- to the pain defense structures, 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. Weakness of the antinociceptive system can lead to a person beginning to feel these nociceptive signals, experiencing constant pain, as, for example, in fibromyalgia. At the same time, clinical and instrumental examination does not reveal somatic or neural pathology that can explain chronic pain. This explains the effect of neurotropic drugs (enhancing the inhibitory functions of the central nervous system, activating the antinociceptive system in fibromyalgia. Weakness of the antinociceptive system can lead to chronic pain in clinically obvious pathology of the somatic sphere or nervous system.
It has now been shown that the posterior columns of the spinal cord, the nuclei of the raphe of the central gray matter, the paragigantocellular and gigantocellular nuclei of the reticular formation, the locus coeruleus, the parabrachial nuclei, the substantia nigra, the red and caudate nuclei, the nuclei of the septal region, the tegmentum, the hypothalamus, the amygdala, the specific and nonspecific nuclei of the thalamus, the frontal, motor and somatosensory cortex of the cerebral hemispheres, and the cerebellum participate in providing analgesia (the work of the antinociceptive system). There are close bilateral connections between these structures. Activation of the above structures suppresses the activity of nociceptive neurons at various levels of the central nervous system, with the neurons of the posterior horn of the spinal cord experiencing the greatest inhibitory effect.
In antinociception, the greatest importance is given to the opioidergic, monoaminergic (serotonin, norepinephrine) systems. Drugs that activate these mediator systems can be used in the treatment of acute and chronic pain (serotonin and norepinephrine reuptake inhibitors, opioids). The opioid system begins to control nociception starting from the terminals of A-sigma and C-afferents, on which opiate receptors are found. Endogenous opioids are endorphins and enkephalins, which have a morphine-like effect on these receptors. The GABA-ergic system also actively participates in the mechanisms of pain sensitivity regulation. Endogenous cannabinoids (anandamide and glycerol arachidonate) also play a significant role.
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