Taken together, our results indicate that the DH/Vc transmits nociceptive information to the PeF via the lateral PB, suggesting the involvement of ORX neurons in the pain pathway.
Moreover, the possible mechanisms contributing to this relationship as endogenous pain modulation, inflammation, affect, mood and other states, the role of different endogenous substances (dopamine, orexin, melatonin, vitamin D) as well as other lesser known such as cyclic alternating pattern among others, will be explored.
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.
This study was carried out to investigate the effects of intrathecal administration of orexin-1 receptor antagonist (SB-334867) in the spinal antinociception induced by intra-LH administration of carbachol (cholinergic receptor agonist) in both early and late phases of pain related behaviors in formalin test.
Our findings suggest that orexin-A is more potent than duloxetine in relieving pain CIPN pain and its analgesic effect is mediated by orexin type-1 receptors.
Furthermore we studied effects of histamine H1 and H2 receptor antagonists on orexin A-produced antinociception in C57BL/6 mice.The antinociceptive effects of i.c.v. orexin A were greater in histamine H1 receptor or H2 receptor knockout mice than in the wild-type mice in all four assays of pain.