Opioid action: Anti-hyperalgesic effects of delta opioid receptor agonists in a model of neuropathic pain

Abstract

Pharmacological evidence supports the involvement of the Delta opioid receptor in antinociception. However, its role in the treatment of neuropathic (NP) pain remains largely unknown. In the present study, we examined the role of delta opioid receptors in an animal model of peripheral nerve injury (PNI). Rats (225-250 g) underwent chronic constriction of the sciatic nerve in accordance with the Mosconi/Kruger model. A cold water test was employed to assess cold hyperalgesia prior to and at various intervals following peripheral nerve injury. Neuropathic rats developed cold hyperalgesia as early as two days following surgery and this sensitivity persisted for the two week testing period. Sham animals did not respond in the testing paradigm employed. The effects of a selective delta opioid receptor agonist were assessed on day 14 following PNI. Intrathecal administration of [D-Ala2]-Deltorphin II (30ug), produced a significant increase in the latency to respond to the noxious cold compared to pre-drug values. Western blotting experiments on dorsal spinal cord segments of day 14 NP rats revealed significantly higher total delta opioid receptor protein levels ipsilateral to nerve injury compared to the contralateral side. These data suggest that delta opioid receptor agonists are a potential therapeutic target for drug development in treating neuropathic pain.