Orexin-A, an hypothalamic peptide with analgesic properties

The hypothalamic peptide orexin-A and the orexin-1 receptor are localized in areas of the brain and spinal cord associated with nociceptive processing. In the present study. localization was confirmed in the spinal cord and demonstrated 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 nociception and hyperalgesia. The efficacy of oresin-A was similar to that of morphine ill the 50 degreesC hotplate test and the carrageenan-induced thermal hyperalgesia test. However. involvement of the opiate system in these effects 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 circumstances. These data demonstrate that the orexinergic system has a potential role in the modulation of nociceptive transmission. (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.