Activation of peripheral kappa opioid receptors inhibits capsaicin-inducedthermal nociception in rhesus monkeys

8-Methyl-N-vanillyl-6-nonenamide (capsaicin) was locally applied in the tai l of rhesus monkeys to evoke a nociceptive response, thermal allodynia, whi ch was manifested as reduced tail-withdrawal latencies in normally innocuou s 46 degrees C water. Coadministration of three kappa opioid ligands, U50,4 88 (3.2-100 mu g), brematocine (0.1-3.2 mu g), and dynorphin A(1-13) (3.2-1 00 mu g), with capsaicin in the tail dose-dependently inhibited capsaicin-i nduced allodynia. This local antinociception was antagonized by a small dos e of an opioid antagonist, quadazocine; (0.32 mg), applied in the tail; how ever, this dose of quadazocine injected s.c. in the back did not antagonize local U50,488. Comparing the relative potency of either agonist or antagon ist after local and systemic administration confirmed that the site of acti on of locally applied kappa opioid agonists is in the tail. In addition, lo cal nor-binaltorphimine (0.32 mg) and oxilorphan (0.1-10 mu g) antagonist s tudies raised the possibility of kappa opioid receptor subtypes in the peri phery, which indicated that U50,488 produced local antinociception by actin g on kappa(1) receptors, but bremazocine acted probably on non-kappa(1) rec eptors. These results provide functional evidence that activation of periph eral kappa opioid receptors can diminish capsaicin-induced allodynia in pri mates. This experimental pain model is a useful tool for evaluating periphe rally antinociceptive actions; of kappa agonists without central side effec ts and suggests new approaches for opioid pain management.