Analgesic Effect of Intrathecal Administration of Orexin on Neuropathic Pain in Rats

Abstract

Orexin-A, a hypothalamic peptide found in the neurons of the lateral hypothalamus, has been shown to modulate pain. We examined whether orexin could alleviate heat-evoked hyperalgesia in rats caused by chronic constriction injury (CCI) of the sciatic nerve. Orexin-A, orexin-B, the vehicle, or orexin-A-antiserum was intrathecally administered to CCI rats. Paw withdrawal latency (PWL) was measured from 30 to 300 minutes after injection, which was repeated for 2 days. Orexin-A administration normalized ΔPWL (PWL in the CCI side minus PWL in the control side) and inhibited heat-evoked hyperalgesia in CCI rats, while orexin-A antiserum inhibited the normalization of heat-evoked hyperalgesia caused by orexin-A two-fold. In contrast, orexin-B had no significant effect. These results suggest that orexin-A may be applicable for treatment of neuropathic pain.