The role of delta-opioid receptor subtypes in neuropathic pain

A large body of evidence suggests an important role of delta -opioid recept or agonists in antinociception at the level of the spinal cord. Our study w as undertaken to analyse the spinal antinociceptive and antiallodynic effec ts of delta (1)- and delta (2)-opioid receptor agonists and antagonist afte r their acute and chronic intrathecal administration in a neuropathic pain model in the rat. In rats with a crushed sciatic nerve, the delta (1)-opioi d receptor agonist [D-Pen(2), D-Pen(5)]enkephalin (DPDPE, 5-25 mug i.t.) an d the delta (2)-opioid receptor agonist deltorphin II (1.5-25 mug i.t.) dos e dependently antagonized the cold-water allodynia which developed after sc iatic nerve injury. These effects of DPDPE were antagonized by 7-benzyliden enaltrexon (BNTX, 1 mug i.t.) while the effects of deltorphin II were antag onized by 5' naltrindole izotiocyanate (5' NTII, 25 mug i.t.). Both agonist s had a dose-dependent, statistically significant effect on the tail-flick latency in two tests, with focused light and cold water. Chronic administra tion of DPDPE (25 mug i.t.) and deltorphin II (15 mug i.t.) resulted in sig nificant prolongation of the reaction time determined on days 2, 4 and 6 po st-injury. In conclusion, our results show an antiallodynic and antinocicep tive action of DPDPE and deltorphin II at the spinal cord level, which sugg ests that both delta -opioid receptor subtypes play a similar role in neuro pathic pain. This indicates that not only delta (1)- but also delta (2)-opi oid receptor agonists can be regarded as potential drugs for the therapy of neuropathic pain. (C) 2001 Elsevier Science B.V. All rights reserved.