Role of Orexin in the Tolerance and Physical Dependence to Morphine

Although opioid drugs cause analgesia and more effective in treatment of pain but, its utility is hindered by the development of tolerance to its analgesic effects. Orexin A and B (hypocretin 1 and 2) discovered in 1998 and projected to large areas of the brain regions involved in the tolerance and dependence to morphine. The attenuated withdrawal syndrome seen in orexinknock-out mice suggests that such regulation of orexin neurons may be an important contributor to morphine physical dependence and to the expression of withdrawal. This systematic review conducted on articles published on orexin from 1998 to 2012 in the following electronic databases: Medline, Pubmed, ISI and Scopus by using keywords including morphine, orexin, tolerance and dependence. Although morphine-tolerance tended to develop in response to repeated injections of morphine, pre-treatment of OXR1 antagonist prevented this effect, causing a delay in the development of morphine-tolerance. Moreover, co-administration of orexin receptor 1 antagonist with morphine significantly decreased the somatic signs of withdrawal.This suggested development of orexin receptor antagonists could prevent the development of tolerance and dependence to morphine.