Role of orexin receptors within the dentate gyrus of the hippocampus in antinociception induced by chemical stimulation of the lateral hypothalamus in the tail-flick test as a model of acute pain in rats

Abstract

The dentate gyrus (DG) as a part of the hippocampal formation is considered one of the brain areas involved in pain perception. The orexin neurons in the lateral hypothalamus (LH) also show connections to regions engaged in the circuitry of pain modulation and many studies have shown their potential to alter pain transmission through the nervous system. However, the role of orexin receptors (OXRs) of the DG in mediation of antinociceptive responses induced by the LH stimulation in rats has not yet been investigated. Hence, the present study was an attempt to examine the role of OXRs located within the DG in the pain modulation induced by chemical stimulation of the LH. Adult male Wistar rats weighing 220–250 g were unilaterally implanted with two separate cannulae into the LH and DG. Intra-DG administration of the orexin-1 receptor (OX1R) antagonist, SB334867 or the orexin-2 receptor (OX2R) antagonist, TCS OX2 29 was performed just 5 min before intra-LH carbachol microinjection. Antinociceptive effects were measured using the tail-flick apparatus. The results showed that OX1R and OX2R antagonists dose-dependently decreased the antinociceptive effect of carbachol. In addition, the effective dose of SB334867 was lesser than that of TCS OX2 29, which indicates the more prominent role of OX1R of the DG in carbachol-induced antinociception. None of the antagonists had any significant effect when administrated without intra-LH carbachol microinjection. It seems to be a neural circuit includes the LH and DG, which plays a major role in the neural basis of pain modulation.