Intrathecal neostigmine but not sympathectomy, relieves mechanical allodynia in a rat model of neuropathic pain

Introduction: Pain resulting from a usually nonpainful stimulus (allodynia) is a common characteristic of neuropathic pain. Among animal models of allodynia, tight ligature of lumbar spinal nerves has been of special interest because it has been reported to be relieved by sympathectomy, The purpose of this study was to determine whether spinal analgesic agents, which have opposite effects on sympathetic nervous system activity (clonidine decreases it and neostigmine increases it), have differing efficacy in this model. Methods: Male Sprague-Dawley rats were anesthetized, and the left L5 and L6 spinal nerves were ligated. At least 2 weeks later, a lumbar intrathecal or jugular intravenous catheter was Inserted. Withdrawal threshold to mechanical stimulation of the hind paw was determined by application of von Frey filaments before surgery; after surgery; after intrathecal injection of clonidine, neostigmine, or their combination; after intravenous injection of phentolamine or guanethidine; and after surgical sympathectomy. Results: Spinal nerve ligation reduced withdrawal threshold ipsilateral to the lesion. 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, Neither chemical nor surgical sympathectomy altered allodynia, Discussion: These results disagree with previous observations that mechanical allodynia in this animal model depends on sympathetic nervous system activity. Therefore, intrathecally administered analgesic agents, one that reduces sympathetic outflow from the spinal cord (clonidine) and one that increases it (neostigmine), were similarly effective in this model.