Modulation of nociception by medial pre-optic area orexin a receptors and its relation with morphine in male rats

• MPOA (medial pre-optic area) is a site implicated in orexin A involves in nociception.
• Orexin A has an analgesic effect after injection into the MPOA.
• The stimulating effect of orexin receptors injected into the MPOA on pain modulation is time dependent.
• The injection of orexin into the MPOA alongside with morphine has additive analgesic effect.

IntroductionRecent studies have shown that medial pre-optic area (MPOA) of hypothalamus are involved in nociception. Orexin A (hypocretin 1) has been found to have numerous applications including pain modulation. However, the role of orexin A receptors in the MPOA on the nociception has not been yet studied. Therefore, the aim of the present study is to investigate the effect of orexin A microinjection on MPOA on the nociception transmission and morphine induced analgesia in adult male rats.MethodsUsing stereotaxic surgery, a cannula was implanted at a site 1 mm above the MPOA in the anesthetized rats. After the recovery period, tail-flick (TF) latency was measured as 0, 15, 30, 45 and 60 min following the onset of two experimental protocols. Two experiments were carried out. Experiment 1: The male rats received intra-MPOA of 25, 100, 1000, 10000 pmol/0.5 μl orexin A or 0.5 μl of aCSF (control, just 5 min before the TF assay. Experiment 2: The aim of this experiment was to examine the effect of orexin microinjection into MPOA on morphine analgesia (3 mg/kg, s.c). Morphine was administered 30 min before orexin A intra-MPOA microinjection (four doses similar to experiment 1) or aCSF, then TF latency was measured.ResultsThe results indicated that microinjection of orexin A into the MPOA showed anti-nociceptive effect in a time-dependent manner. Dose response curve results also revealed that the maximum effective dose of orexin A injection into MPOA for pain inhibition is 1000 pmol/0.5 μl. Co-administration of systemic morphine and orexin into the MPOA has additive analgesia with different time course compared morphine or orexin alone.ConclusionIt can be concluded that MPOA OrexinA receptors play an important role in the modulation of pain in normal and morphine treated male rats.