INTRATHECAL NEOSTIGMINE BUT NOT SYMPATHECTOMY, RELIEVES MECHANICAL ALLODYNIA IN A RAT MODEL OF NEUROPATHIC PAIN

Introduction: Pain resulting from a usually nonpainful stimulus (allod ynia) is a common characteristic of neuropathic pain. Among animal mod els of allodynia, tight ligature of lumbar spinal nerves has been of s pecial interest because it has been reported to be relieved by sympath ectomy, The purpose of this study was to determine whether spinal anal gesic agents, which have opposite effects on sympathetic nervous syste m activity (clonidine decreases it and neostigmine increases it), have differing efficacy in this model. Methods: Male Sprague-Dawley rats w ere anesthetized, and the left L5 and L6 spinal nerves were ligated. A t least 2 weeks later, a lumbar intrathecal or jugular intravenous cat heter was Inserted. Withdrawal threshold to mechanical stimulation of the hind paw was determined by application of von Frey filaments befor e surgery; after surgery; after intrathecal injection of clonidine, ne ostigmine, or their combination; after intravenous injection of phento lamine or guanethidine; and after surgical sympathectomy. Results: Spi nal nerve ligation reduced withdrawal threshold ipsilateral to the les ion. This allodynia was relieved by clonidine (50% block of allodynia at 20 +/- 1.2 mu g and neostigmine (50% block of allodynia at 2 +/- 0. 1 mu g, and they interacted synergistically to block allodynia, Neithe r chemical nor surgical sympathectomy altered allodynia, Discussion: T hese results disagree with previous observations that mechanical allod ynia in this animal model depends on sympathetic nervous system activi ty. Therefore, intrathecally administered analgesic agents, one that r educes sympathetic outflow from the spinal cord (clonidine) and one th at increases it (neostigmine), were similarly effective in this model.