Intra-CA1 injection of orexin receptors antagonism attenuates the stress-induced analgesia in a rat acute pain model

Orexins or hypocretins are excitatory neuropeptides predominantly produced by neuronal clusters in the lateral hypothalamus. The orexinergic system's involvement in pain modulation makes it a candidate for pain control alternative to the opioid system. Moreover, orexin-1 and orexin -2 receptors (OX1r and OX2r, respectively) play a role in responsiveness to stressful stimuli. Some evidence indicates that the Cornu Ammonis 1 (CA1) region of the hippocampus potentially participates in the modulation of both pain and stress. In quest of better understanding the interaction between orexin receptors and stress-induced analgesia (SIA), The present study examined the involvement of OX1r and OX2r within the CA1 in response to acute pain after exposure to forced swim stress (FSS) for a 6-min period. Adult male Wistar rats received different doses of OX1r antagonist (SB334867; 1, 3, 10, and 30 nmol), OX2r antagonist (TCS OX2 29; 3, 10, 30 and 100 nmol), or vehicle (0.5 μl DMSO) through an implanted cannula. After that, animals individually experienced acute pain by performing the tail-flick test. Results indicated that FSS produces antinociceptive responses in the tail-flick test. Blockade of both orexin receptors within the CA1 region attenuated the analgesic effect of FSS. The antinociceptive effect of swim stress was prevented by lower doses of SB334867 than TCS OX2 29. These findings show that the orexinergic system might be partially involved in the SIA via the OX1 and OX2 receptors in the hippocampal CA1 region.