Pain behavior and response properties of spinal dorsal horn neurons following experimental diabetic neuropathy in the rat: Modulation by nitecapone, a COMT inhibitor with antioxidant properties

We attempted to characterize a spinal neuronal correlate of painful neuropa thy induced by diabetes mellitus (DM), Pain behavior and response propertie s of spinal dorsal horn neurons were determined in rats with a streptozocin -induced DM, A catechol-O-methyltransferase inhibitor with potent antioxida nt properties, nitecapone, was used in an attempt to attenuate neuropathic symptoms. Behaviorally DM induced mechanical hypersensitivity that was mark edly attenuated by oral treatment with nitecapone, The antihyperalgesic eff ect of nitecapone was not reversed by naloxone, an opioid antagonist, or at ipamezole, an alpha -2-adrenoceptor antagonist. Electrophysiological record ings performed in pentobarbitone-anesthetized animals revealed that the mos t distinct abnormality in response properties of spinal dorsal horn wide-dy namic range (WDR) neurons was the increase in their spontaneous activity ob served in untreated but not in nitecapone-treated DM rats. Conditioning ele ctrical stimulation and a lidocaine block of the rostroventromedial medulla (RVM) had a similar modulatory effect on evoked responses of spinal dorsal horn WDR neurons in all experimental groups. The response properties of sp inal dorsal horn nociceptive-specific or low-threshold mechanoreceptive neu rons were not markedly different between the experimental groups, The resul ts indicate that increased spontaneous activity in spinal dorsal horn WDR n eurons may be causally related to behaviorally observed mechanical hypersen sitivity in DM. Attenuation of the increased spontaneous activity in WDR ne urons may explain the antihyperalgesic effect by nitecapone, due to naloxon e- and alpha -2-adrenoceptor-insensitive mechanisms. DM or nitecapone treat ment did not produce significant changes in phasic or tonic descending pain regulation originating in the RVM. (C) 2001 Academic Press.