THE ROLE OF PERIPHERAL MU-OPIOID RECEPTORS IN THE MODULATION OF CAPSAICIN-INDUCED THERMAL NOCICEPTION IN RHESUS-MONKEYS

Capsaicin produces burning pain, followed by nociceptive responses, su ch as allodynia and hyperalgesia in humans and rodents. In the present study, when administered subcutaneously into the tail of rhesus monke ys, capsaicin (0.01-0.32 mg) dose-dependently produced thermal allodyn ia manifested as reduced tail-withdrawal latencies in 46 degrees C wat er, from a maximum value of 20 sec to approximately 2 sec. Coadministr ation of selective mu opioid agonists, fentanyl (0.003-0.1 mg) and (D- Ala(2),N-Me-Phe(4), Gly(5)-ol)-enkephalin (0.001-0.03 mg), dose-depend ently inhibited capsaicin-induced allodynia. This local antinociceptio n was antagonized by small doses of opioid antagonists, quadazocine (0 .03 mg) and quaternary naltrexone (1 mg), applied locally in the tail. However, these doses of antagonists injected s.c. in the back did not antagonize local fentanyl. Comparing the relative potency of either a gonist or antagonist after local and systemic administration confirmed that the site of action of locally applied mu opioid agonists is in t he tail. These results provide evidence that activation of peripheral mu opioid receptors can diminish capsaicin-induced allodynia in primat es. This experimental pain model could be a useful tool for evaluating peripherally acting antinociceptive agents without central side effec ts and enhance new approaches to the treatment of inflammatory pain.