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Introduction: Orexin-A and B (Hypocretin 1 and 2) are neuropeptides that are mostly expressed in the posterior and lateral hypothalamus (LH). Intracisternal (ICV) and intratechal (IT) injections of orexin-A (hypocretin-1) have been shown to elicit analgesic responses in formalin test. However, the locations of central sites that may mediate these effects have not been clearly elucidated. Orexin-containing fibers are projected to periaqueductal gray matter (PAG), which is involved in pain modulation. Methods: Behavioral study was done on male Sprague Dawley rats (200-300 g) in formalin induced nociceptive behaviour. Results: Intra-PAG microinjection of orexin-A produced a dose-dependent inhibition of formalin-evoked behaviour in interphase and phase 2, but not in phase 1, indicating an antinociceptive role of exogenous orexin-A in the PAG. Analgesic effect of orexin-A was less than and specific to inter- and late phase of formalin test, when compared with that of morphine (5 μg/0.5μl) after intra-PAG administration. Conclusion: The obtained results suggest that orexin-A plays an anti-nociceptive role in PAG, on the interphase and late phase of formalin test in rats. So it is possible that orexin-A might be involved in the mechanisms of inter- and last phases of formalin induced behaviours.

Keywords: orexin-A, analgesic, periaqueductal gray matter, formalin test, morphine

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