• Edgar T Walters.
• Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA. Electronic address: edgar.t.walters@uth.tmc.edu.
• Auton Neurosci. 2018 Jan 1; 209: 79-89.

AbstractAutonomic dysreflexia (AD) and neuropathic pain occur after severe injury to higher levels of the spinal cord. Mechanisms underlying these problems have rarely been integrated in proposed models of spinal cord injury (SCI). Several parallels suggest significant overlap of these mechanisms, although the relationships between sympathetic function (dysregulated in AD) and nociceptive function (dysregulated in neuropathic pain) are complex. One general mechanism likely to be shared is central sensitization - enhanced responsiveness and synaptic reorganization of spinal circuits that mediate sympathetic reflexes or that process and relay pain-related information to the brain. Another is enhanced sensory input to spinal circuits caused by extensive alterations in primary sensory neurons. Both AD and SCI-induced neuropathic pain are associated with spinal sprouting of peptidergic nociceptors that might increase synaptic input to the circuits involved in AD and SCI pain. In addition, numerous nociceptors become hyperexcitable, hypersensitive to chemicals associated with injury and inflammation, and spontaneously active, greatly amplifying sensory input to sensitized spinal circuits. As discussed with the aid of a preliminary functional model, these effects are likely to have mutually reinforcing relationships with each other, and with consequences of SCI-induced interruption of descending excitatory and inhibitory influences on spinal circuits, with SCI-induced inflammation in the spinal cord and in DRGs, and with activity in sympathetic fibers within DRGs that promotes local inflammation and spontaneous activity in sensory neurons. This model suggests that interventions selectively targeting hyperactivity in C-nociceptors might be useful for treating chronic pain and AD after high SCI.Copyright © 2017 Elsevier B.V. All rights reserved.

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