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Pain Pathways

(ĐTĐ) – Pain is a central perception of multiple primary sensory modalities. This interpretive function is complex, involving psychological, neuroanatomic, neurochemical, and neurophysiologic factors of both the pain stimulus and the memory of past pain experiences.

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The peripheral mechanisms for sensing and modulating pain have been extensively studied during the past 30 years. The pathways for pain sensation, from the initial stimulus of the nociceptors to the central nervous system, are summarized in Figure-1. There appear to be several descending systems that play a role in control of the modification of the ascending pain pathways, which are summarized in Figure-2.

Pain Pathways

FIGURE-1. Central nervous system structures that modify ascending pain pathways. H, hypothalamus; IL, intralaminar thalamic nuclei; L, limbic system.

Polymodal nociceptors respond to stimuli that damage tissue. This stimulation results in impulses ascending in the A-delta or C fibers to the marginal layers of the dorsal horn of the spinal cord. The A-delta fibers primarily synapse in laminae I and V, whereas C fibers synapse primarily in lamina II. Deeper regions of the dorsal horn may be polysynaptically involved in the processing of noxious stimuli.

Pain Pathways

FIGURE-2. Ascending pathways for pain sensation from nociceptors to the central nervous system. H, hypothalamus; IL, intralaminar thalamic nuclei; L, limbic system; PT, posterior thalamic nuclei; VPL, ventral posterolateral thalamic nuclei.

The major ascending nociceptive pathways are the spinothalamic and spinoreticular tracts, which involve both oligosynaptic and polysynaptic neurons. These oligosynaptic pathways are fast conducting, with discrete somatotopic organization resulting in rapid transmission of nociceptive information regarding site, intensity, and duration of stimulus. Further, the oligosynaptic tracts provide somatic information by way of the posterior ventral nuclei of the thalamus to the postcentral cortex. The sensory discriminatory characteristics are delineated from the neospinothalamic portion of the lateral spinothalamic tract and the nonproprioceptive portion of the dorsal columns.

Polysynaptic pathways are slow conducting, with a lack of somatotopic organization resulting in poor localization as well as dull aching and burning sensations. The nociceptive impulses transmitted through this system result in suprasegmental reflex responses related to ventilation, circulation, and endocrine function. Pathways contributing to this slowconducting system are the paleospinothalamic tract, spinoreticular, spinocollicular, and the dorsal intercornual, as well as the spinomesencephalic tracts. The polysynaptic tracts form the brain stem reticular activating system with projections to the medial and interlaminar nuclei of the thalamus. From these nuclei, diffuse radiation occurs to the cerebral cortex, limbic system, and basal ganglia.

There are multiple levels of processing and convergence of nociceptive information in its ascending transmission to the cerebral cortex. In addition, there appear to be several descending pain control systems that play a role in the control and modification of the ascending pain pathways. The most complete studies have been of the periaqueductal gray (PAG) region of the midbrain. Stimulation of the PAG neurons and the subsequent descending impulses result in release of endogenous opioids at the nucleus raphe magnus (NRM) and nucleus locus ceruleus (NLC). Endogenous opioids activate the serotonergic cells in the NRM and norepinergic neurons in the NLC. The axons of both of these monoaminergic neurons descend in the dorsolateral tract to interneurons, predominantly in laminae I, II, and V. These monoamines activate opioid-secreting interneurons. The morphine-like transmitter released may vary, depending on what type of receptor in the periphery has been activated. Both A-delta and C afferent fibers are inhibited by descending influences in the dorsal horn. The opioid inhibitory interneurons may be influenced by intersegmental and descending pathways, but the intersegmental and segmental mechanisms have not been established. These interneurons may function either by presynaptic inhibition on the terminals with the primary nociceptive afferents preventing the release of substance P or by postsynaptic inhibition on second-order neurons. Cells in the raphe magnus are activated by ascending sensory pathways transmitted to the reticular formation as well as by descending input from cells in the PAG region.

Other descending monoamine systems include locus ceruleus to the dorsal horn interneurons, nucleus reticularis, magnicellularis to the dorsal horn interneurons, and the mesencephalic lateral reticular formation to the dorsal horn interneurons. It has been suggested that monoamines are involved with supraspinal and spinal nociceptive mechanisms. Hormonally based descending pathways have been described but are poorly understood.

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