Activation of Peripheral k Opioid Receptors Inhibits Capsaicin- Induced Thermal Nociception in Rhesus Monkeys1

8-Methyl-N-vanillyl-6-nonenamide (capsaicin) was locally ap-plied in the tail of rhesus monkeys to evoke a nociceptive response, thermal allodynia, which was manifested as reduced tail-withdrawal latencies in normally innocuous 46°C water. Coadministration of three k opioid ligands, U50,488 (3.2–100 mg), bremazocine (0.1–3.2 mg), and dynorphin A(1–13) (3.2–100 mg), with capsaicin in the tail dose-dependently inhibited cap-saicin-induced allodynia. This local antinociception was antag-onized by a small dose of an opioid antagonist, quadazocine; (0.32 mg), applied in the tail; however, this dose of quadazocine injected s.c. in the back did not antagonize local U50,488. Comparing the relative potency of either agonist or antagonist after local and systemic administration confirmed that the site of action of locally applied k opioid agonists is in the tail. I