Pathologic hyperexcitability of sensory neurons can, conceivably, result from downregulation of voltage-gated potassium (Kv) channels whose function is to repolarize the cell membrane (197,198). Some of these channels such as Kv1.4 appear to be selectively expressed by nociceptive afferent neurons (199). TNBSA-induced ileitis increases the excitability and conduction velocity in nociceptive DRG neurons, a change that is in part attributed to a decrease in the transient A-type and sustained outward rectifier K+ currents (185,186). Acetic acid-induced gastric ulceration leads to a similar rise of excitability and fall of A-type K+ current density in spinal and vagal afferents innervating the rat stomach (200). Pharmacologic enhancement of A-type K+ currents would hence be expected to counteract hyperalgesia, a mode of action whereby compound KW-7158 depresses the excitability of pelvic afferents and inhibits inflammation-induced bladder overactivity (201).
Was this article helpful?