Antihyperalgesic activity of epibatidine in the formalin model of facial pain

A growing body of evidence supports a nicotinic cholinergic approach to pai n management, as neuronal nicotinic receptor agonists have shown efficacy a cross animal models of both inflammatory and neuropathic pain. However, mos t of these investigations have focused on the spinal system, and there is t o date no report of nicotinic receptor-mediated antinociception in any pain model involving the trigeminal field of innervation. Thus, the purpose of the present studies was to evaluate whether the neuronal nicotinic receptor agonist epibatidine possesses antihyperalgesic activity in the formalin mo del of facial pain. Adult, male, Sprague-Dawley rats received a 50-mul, sub cutaneous injection of 5% formalin into one vibrissal pad and the consequen t, facial grooming behavior was monitored. Consistent with previous investi gations using the formalin model, animals exhibited two periods of noeifens ive grooming: (1) an acute phase that began immediately, peaked at 3 min an d almost completely abated by 6 min, and (2) a tonic phase that began betwe en 6 and 9 min, peaked at 21 min and slowly diminished over the ensuing 24 min. The subcutaneous administration of epibatidine (1-5 mug/kg) 5 min prio r to the formalin injection led to a significant, dose-dependent reduction of both the acute and tonic phases of hyperalgesia. Separate groups of anim als receiving epibatidine either 15, 30 or 60 min prior to the formalin inj ection exhibited a progressively diminishing antihyperalgesic response that was no longer significant in either phase by 30 min. Finally, pretreatment with the selective neuronal nicotinic receptor antagonist mecamylamine com pletely abolished the antihyperalgesic effect of epibatidine in both phases . Taken together, these studies demonstrate that in both the acute and toni c phases of the formalin model of facial pain, epibatidine produces a neuro nal nicotinic receptor-mediated antihyperalgesia that is both dose- and tim e-dependent. These results support the rationale for exploring the clinical efficacy of nicotinic agonists as analgesics to treat certain types of tri geminal pain in humans. (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.