Spinal administration of a δ opiold receptor agonist attenuates hyperalgesia and allodynia in a rat model of neuropathic pain

Neuropathic (NP) pain is a debilitating chronic pain disorder considered by some to be inherently resistant to therapy with traditional analgesics. Indeed, mu opioid receptor (OR) agonists show reduced therapeutic benefit and their long term use is hindered by the high incidence of adverse effects. However, pharmacological and physiological evidence increasingly suggests a role for delta OR agonists in modulating NP pain symptoms. In this study, we examined the antihyperalgesic and antiallodynic effects of the spinally administered delta OR agonist, D-[Ala(2), Glu(4)]deltorphin II (deltorphin II), as well as the changes in delta OR expression, in rats following chronic constriction injury (CCI) of the sciatic nerve. Rats with CCI exhibited cold hyperalgesia and mechanical allodynia over a 14-day testing period. Intrathecal administration of deltorphin II reversed cold hyperalgesia on day 14 and dose-dependently attenuated mechanical allodynia. The effects of deltorphin 11 were mediated via activation of the delta OR as the effect was antagonized by co-treatment with the delta-selective antagonist, naltrindole. Western blotting experiments revealed no changes in delta OR protein in the dorsal spinal cord following CCI Taken together, these data demonstrate the arnihyperalgesic and antiallodynic effectiveness of a spinally administered delta OR agonist following peripheral nerve injury and support further investigation of delta ORs as potential therapeutic targets in the treatment of NP pain. (c) 2006 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.