Spinal administration of a δ opioid 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, μ 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 δOR agonists in modulating NP pain symptoms. In this study, we examined the antihyperalgesic and antiallodynic effects of the spinally administered δOR agonist, d-[Ala2, Glu4]deltorphin II (deltorphin II), as well as the changes in δOR 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 II were mediated via activation of the δOR as the effect was antagonized by co-treatment with the δ-selective antagonist, naltrindole. Western blotting experiments revealed no changes in δOR protein in the dorsal spinal cord following CCI. Taken together, these data demonstrate the antihyperalgesic and antiallodynic effectiveness of a spinally administered δOR agonist following peripheral nerve injury and support further investigation of δORs as potential therapeutic targets in the treatment of NP pain.