Agmatine attenuates neuropathic pain in sciatic nerve ligated rats: Modulation by hippocampal sigma receptors

Present study investigated the influence of the sigma (sigma(1) and sigma(2)) receptors within hippocampus on the agmatine induced antinociception in neuropathic rats. Animals were subjected to sciatic nerve ligation for induction of neuropathic pain and observed the paw withdrawal latency in response to thermal hyperalgesia, cold allodynia and the mechanical hyperalgesia. Intrahippocampal (i.h.) as well as intraperitoneal (i.p.) administration of agmatine attenuated neuropathic pain in sciatic nerve ligated rats. Intrahippocampal administration of sigma(1) agonist (+)-pentazocine or sigma(2) agonist PB28 sensitized whereas, sigma(1) antagonist BD1063 or sigma(2) antagonist SM21 potentiated antinociceptive effect of agmatine. The behavioral effects correlated with hippocampal tumor necrosis factor-alpha (TNF-alpha) levels observed by western blot analysis. These results suggest that both the sigma(1) and sigma(2) receptor subunits within hippocampus play an important role in antinociceptive action of agmatine against neuropathic pain. (C) 2013 Elsevier B.V. All rights reserved.