Local administration of delta9-tetrahydrocannabinol attenuates capsaicin-induced thermal nociception in rhesus monkeys: a peripheral cannabinoid action.
BACKGROUND
Cannabinoids can reduce nociceptive responses by acting on peripheral cannabinoid receptors in rodents.


OBJECTIVE
The study was conducted to evaluate the hypothesis that local administration of delta9-tetrahydrocannabinol (delta9-THC) can attenuate capsaicin-induced nociception in rhesus monkeys.


METHODS
Capsaicin (100 microg) was applied locally in the tail of rhesus monkeys to evoke a nociceptive response, thermal allodynia, in normally innocuous 46 degrees C water. delta9-THC (10-320 microg) was coadministered with capsaicin in the tail to assess local antinociceptive effects. In addition, a local antagonism study was performed to confirm the selectivity of delta9-THC action.


RESULTS
delta9-THC dose-dependently inhibited capsaicin-induced allodynia. This local antinociception was antagonized by small doses (10-100 microg) of the cannabinoid CB1 antagonist, SR141716A, applied in the tail. However, 100 microg SR141716A injected subcutaneously in the back did not antagonize local delta9-THC.


CONCLUSIONS
These results indicate that the site of action of locally applied delta9-THC is in the tail. It provides functional evidence that activation of peripheral cannabinoid CB1 receptors can attenuate capsaicin-induced thermal nociception in non-human primates and suggests a new approach for cannabinoids in pain management.
Ko
M C
MC
Department of Pharmacology, University of Michigan, Medical School, Ann Arbor 48109-0632, USA. mko@umich.edu
Woods
J H
JH
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002186:Cannabinoids / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D002211:Capsaicin / Q000494:pharmacology; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D008253:Macaca mulatta; D008297:Male; D010147:Pain Measurement / Q000187:drug effects*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D000077285:Rimonabant
D018712:Analgesics, Non-Narcotic; D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol; D000077285:Rimonabant; D002211:Capsaicin