Orexin-A, an hypothalamic peptide with analgesic properties

The hypothalamic peptide orexin-A and the orexin-1 receptor are localized i n areas of the brain and spinal cord associated with nociceptive processing . In the present study. localization was confirmed in the spinal cord and d emonstrated in the dorsal root ganglion for both orexin-A and the orexin-1 receptor. The link with nociception was extended when orexin-A was shown to be analgesic when given i.v. but not s.c. in mouse and rat models of nocic eption and hyperalgesia. The efficacy of oresin-A was similar to that of mo rphine ill the 50 degreesC hotplate test and the carrageenan-induced therma l hyperalgesia test. However. involvement of the opiate system in these eff ects was ruled out as they were blocked by the orexin-1 receptor antagonist SE-334867 but not naloxone. Orexin-1 receptor antagonists had no effect in acute nociceptive tests but under particular inflammatory conditions were pro-hyperalgesic. suggesting a tonic inhibitory orexin drive in these circu mstances. These data demonstrate that the orexinergic system has a potentia l role in the modulation of nociceptive transmission. (C) 2001 Internationa l Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.