Effects and consequences of nerve injury on the electrical properties of sensory neurons

Abstract

Nociceptive pain alerts the body to potential or actual tissue damage. By contrast, neuropathic or "noninflammatory" pain, which results from injury to the nervous system, serves no useful purpose. It typically continues for years after the original injury has healed. Sciatic nerve lesions can invoke chronic neuropathic pain that is accompanied by persistent, spontaneous activity in primary afferent fibers. This activity, which reflects changes in the properties and functional expression of Na+, K+, and Ca2+ channels, initiates a further increase in the excitability of second-order sensory neurons in the dorsal horn. This change persists for many weeks. The source of origin of the pain thus moves from the peripheral to the central nervous system. We hypothesize that this centralization of pain involves the inappropriate release of peptidergic neuromodulators from primary afferent fibers. Peptides such as substance P, neuropeptide Y (NPY), calcitonin-gene-related peptide (CGRP), and brain-derived neurotrophic factor (BDNF) may promote enduring changes in excitability as a consequence of neurotrophic actions on ion channel expression in the dorsal horn. Findings that form the basis of this hypothesis are reviewed. Study of the neurotrophic control of ion channel expression by spinal peptides may thus provide new insights into the etiology of neuropathic pain.

Distribution of Peripherally Injected Peptide YY ([125I] PYY (3–36)) and Pancreatic Polypeptide ([125I] hPP) in the CNS: Enrichment in the Area Postrema

“…or intraperitoneal (i.p.) administration of PYY(3-36) on feeding was confirmed in various laboratories independently (Abdulla et al 2003;Challis et al 2003Challis et al , 2004Cox et al 2004;Halatchev et al 2004, Halatchev andCone 2005;Scott et al 2005;Chelikani et al 2005;Moran et al 2005). However, some failed to demonstrate these anorexic actions (Tschop et al 2004).…”

Neuropeptide Y2 receptor protein is present in peptidergic and nonpeptidergic primary sensory neurons of the mouse

“…IB4 ϩ DRG neurons in rats have a higher density of voltage-gated tetrodotoxin-resistant (TTX-R) Na ϩ currents and longer duration action potentials (Stucky and Lewin, 1999), both characteristic features of nociceptive neurons in vivo (Koerber et al, 1988;Traub and Mendell, 1988;Djouhri et al, 1988), and a higher density of voltagegated K ϩ channels, contributing to a higher basal firing threshold and electrogenesis (Vydyanathan et al, 2004). Moreover, axotomy induces an increase in TTX-R Na ϩ channel currents, especially in small neurons (Abdulla et al, 2003). In contrast, IB4…”

Inflammation and nerve fiber interaction in endometriotic pain

“…SP release from sensory neurons is increased after nerve injury [84], which may occur in endometriosis either by a physical interaction with the lesion or by stimulation with inflammatory mediators [13]. Neurokinin 1 receptor (NK1R) is the natural receptor for SP and has recently been identified in endometriotic lesions [22].…”