Spinal orexin A attenuates opioid-induced mechanical hypersensitivity in the rat

Repeated administration of opioid analgesics for pain treatment can produce paradoxical hyperalgesia via peripheral and/or central mechanisms. Thus, this study investigated whether spinally (centrally) administered orexin A attenuates opioid-induced hyperalgesia (OIH). [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), a selective μ-opioid receptor agonist, was used to induce mechanical hypersensitivity and was administered intradermally (4 times, 1-hour intervals) on the rat hind paw dorsum. To determine whether post- or pretreatments with spinal orexin A, dynorphin A, and antidynorphin A were effective in OIH, the drugs were injected through an intrathecal catheter whose tip was positioned dorsally at the L3 segment of the spinal cord (5 μg for all). Mechanical hypersensitivity was assessed using von Frey monofilaments.