Abstract
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°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.
Footnotes
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Send reprint requests to: Dr. James H. Woods, Dept. of Pharmacology, Medical School, University of Michigan, 1301 MSRB III, Ann Arbor, MI 48109-0632.
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↵1 Animals used in these studies were maintained in accordance with the University Committee on the Use and Care of Animals, University of Michigan, and Guidelines of the Committee on the Care and Use of Laboratory Animals of the institute of Laboratory Animal Resources, National Health Council (Department of Health, Education and Welfare, Publication ISBN 0–309-05377–3, revised 1996).
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↵2 Support for this research was provided by USPHS Grant 00254. Preliminary results were presented at the 16th annual meeting of American Pain Society, New Orleans, LA, October 23–26, 1997.
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↵3 Present address: Rockefeller University, New York, NY.
- Abbreviations:
- Capsaicin
- 8-methyl-N-vanillyl-6-nonenamide
- DAMGO
- (d-Ala2,N-Me-Phe4, Gly5-ol)-enkephalin
- D.R.
- dose ratio
- Quadazocine
- WIN 44441–3
- QNTX
- quaternary naltrexone
- %MPE
- %maximum possible effect
- Received December 29, 1997.
- Accepted March 13, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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