Thioperamide-induced Antinociception is Mediated through Endogenous Opioid System in the Dentate Gyrus of Adult Rats

Document Type : Original Article


1 Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

2 Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran


The present study investigated the effects of intra-dentate gyrus microinjection of naloxone (an opioid antagonist) and thioperamide (an antagonist of histamine H3 receptors) in the formalin test in rats. Subcutaneous injection of formalin (50 μl, 2.5 %) in the ventral surface of right hind paw produced a biphasic pattern (first phase: 0-5 min and second phase: 15 - 60 min) of licking/biting and shaking of the injected paw. Intra-dentate gyrus microinjections of thioperamide (2 and 4 μg) significantly (P < 0.05) suppressed the pain responses. Microinjections of naloxone (1, 2 and 4 μg) alone into the dentate gyrus non-significantly increased the intensity of pain. Pretreatment with naloxone (4 μg) significantly (P < 0.05) reversed the antinociceptive effect of thioperamide (4 μg). The results indicated that at the level of the dentate gyrus, blockade of histamine H3 receptors with thioperamide produced an analgesic effect. This thioperamide-induced antinociception may be mediated through the endogenous opioid system.