Central post-stroke pain (CPSP) is one of the secondary diseases of cerebral stroke. However, the detailed mechanism remains unclear. Recently, it is reported that central administration of orexin-A reduces nociceptive responses in inflammatory pain model mouse. In this study, we tested the effect of orexin-A on CPSP model mouse. Male ddY mice (5 weeks old) were subjected to 30 min of bilateral carotid artery occlusion (BCAO). Mechanical allodynia was measured by von Frey filament test. The withdrawal responses to mechanical stimuli were significantly increased on day 3 after BCAO. On day 3 after BCAO, prepro-orexin (orexin precursor) was decreased as compared with sham. The BCAO-induced mechanical allodynia suppressed by the intracerebroventricular (i.c.v.) injection of orexin-A. These effects of orexin-A were inhibited by the intrathecal injection of yohimbine (an adrenaline α2 receptor antagonist) or WAY100635 (a serotonin 5-HT1A receptor antagonist). A c-Fos (a neuronal activation marker) expression was observed in the rostral ventromedial medulla or locus coeruleus after i.c.v. injection of orexin-A. These results suggested that orexin-A plays an important role in the regulation of CPSP mediated by the descending pain control system.