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, such as allodynia and hyperalgesia in humans and rodents. In the present study, when administered subcutaneously into the tail of rhesus monkeys, capsaicin (0.01-0.32 mg) dose-dependently produced thermal allodynia manifested as reduced tail-withdrawal latencies in 46 degrees C water, from a maximum value of 20 sec to approximately 2 sec. Coadministration of selective mu opioid agonists, fentanyl (0.003-0.1 mg) and (D-Ala2,N-Me-Phe4, Gly5-ol)-enkephalin (0.001-0.03 mg), dose-dependently inhibited capsaicin-induced allodynia. This local antinociception 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 agonist or antagonist after local and systemic administration confirmed that the site of action of locally applied mu opioid agonists is in the tail. These results provide evidence that activation of peripheral mu opioid receptors can diminish capsaicin-induced allodynia in primates. This experimental pain model could be a useful tool for evaluating peripherally acting antinociceptive agents without central side effects and enhance new approaches to the treatment of inflammatory pain.
Ko
M C
MC
Department of Pharmacology, University of Michigan, Ann Arbor, USA.
Butelman
E R
ER
Woods
J H
JH
D000818:Animals; D001392:Azocines / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D006358:Hot Temperature; D008253:Macaca mulatta; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy; D017450:Receptors, Opioid, mu / Q000502:physiology*
D001392:Azocines; D004745:Enkephalins; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; D002211:Capsaicin; C035969:quadazocine