Orexin‐A, an hypothalamic peptide with analgesic properties. (SmithKline Beecham Pharmaceuticals, Harlow, Essex, United Kingdom) Pain. 2001;92:81–90.

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 conformed in the spinal cord and demonstrated in the dorsal root ganglion for both orexin‐A and the orexin‐1 receptor. The efficacy of orexin‐A was similar to that of morphine in the 50°C 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 SB‐334867, but not naloxone. Orexin‐1 receptor antagonists had no effect in acute nociceptive tests, but under particular inflammatory conditions were prohyperalgesic, suggesting a tonic inhibitory orexin drive in these circumstances. Conclude that the orexinergic system has a potential role in the modulation of nociceptive transmission.