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

Abstract

Recent 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. Using stereotaxic surgery, a cannula was implanted at a site 1mm above the MPOA in the anesthetized rats. After the recovery period, tail-flick (TF) latency was measured as 0, 15, 30, 45 and 60min following the onset of two experimental protocols. Two experiments were carried out. Experiment 1: The male rats received intra-MPOA of 25, 100, 1000, 10000pmol/0.5μl orexin A or 0.5μl of aCSF (control, just 5min before the TF assay. Experiment 2: The aim of this experiment was to examine the effect of orexin microinjection into MPOA on morphine analgesia (3mg/kg,s.c). Morphine was administered 30min before orexin A intra-MPOA microinjection (four doses similar to experiment 1) or aCSF, then TF latency was measured. The 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 1000pmol/0.5μl. Co-administration of systemic morphine and orexin into the MPOA has additive analgesia with different time course compared morphine or orexin alone. It can be concluded that MPOA OrexinA receptors play an important role in the modulation of pain in normal and morphine treated male rats.