Review articleThe functional anatomy of neuropathic pain
Section snippets
Physiologic activation of the pain pathways
A large number of endogenous substances are released after tissue injury or inflammation, and these can excite or sensitize nociceptive afferents. Some of these mediators act through ligand-gated cation channels (eg, H+, adenosine triphosphate [ATP]), whereas others act via G-protein–coupled receptors (eg, calcitonin gene–related peptide [CGRP], prostaglandins, bradykinin [BK], 5-hydroxytryptamine [5HT], serotonin). Changes in the excitability of nociceptive afferent neurons may result from the
Ascending pain pathways
Noxious stimulation is transmitted to the central nervous system (CNS) by the activation of small-diameter sensory afferent nerves (eg, unmyelinated C-fibers, small-diameter myelinated A-fibers). These neurons have their cell bodies in the dorsal root ganglia (innervating the body), the trigeminal ganglia (innervating the head), and the nodose ganglia (innervating the viscera), and they project to specific laminae of the dorsal spinal cord. C-fibers with cell bodies in the dorsal root ganglia
Cerebral cortex
Stimulation of the somatosensory cortex in monkeys causes inhibition of spinothalamic tract cells [66], [67]. This cortical inhibition acts mainly on responses to innocuous mechanical stimulation, whereas the inhibition produced by stimulation in the PAG or NRM exerts a powerful analgesic effect acting on nociceptive processing [68]. Chronic stimulation of the motor cortex in human beings produces relief of neuropathic pain in a somatotopy-specific fashion, suggesting an important role of the
Factors involved in the generation of neuropathic pain: peripheral and central sensitization
Neuropathic pain is a pathologic process characterized by abnormal nociception induced by a process of sensitization after neural damage (either at a peripheral or central level). There are two main types of sensitization: peripheral sensitization, which acts on the nociceptors, and central sensitization, which can take place at various levels ranging from the dorsal horns to the brain. Both peripheral and central sensitization plays a crucial role in the generation of neuropathic pain. As we
Summary
The generation of neuropathic pain is a complex phenomenon involving a process of peripheral and central sensitization producing enhanced transmission of nociceptive inputs to the brain associated with the loss of discriminatory processing of noxious and innocuous stimuli. This increased flow of abnormally processed nociceptive inputs to the brain may overcome the ability of descending modulatory pathways to produce analgesia, causing further worsening of the pain. Several crucial locations
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