Local administration of Δ9-tetrahydrocannabinol attenuates capsaicin-induced thermal nociception in rhesus monkeys:: a peripheral cannabinoid action

Rationale: Cannabinoids can reduce nociceptive responses by acting on peripheral cannabinoid receptors in rodents. Objectives: The study was conducted to evaluate the hypothesis that local administration of ag-tetrahydrocannabinol (Delta(9)-THC) can attenuate capsaicin-induced nociception in rhesus monkeys. Methods: Capsaicin (100 mu g) was applied locally in the tail of rhesus monkeys to evoke a nociceptive response, thermal allodynia, in normally innocuous 46 degrees C water. Delta(9)-THC (10-320 mu g) 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 Delta(9)-THC action. Results: Delta(9)-THC dose-dependently inhibited capsaicin-induced allodynia. This local antinociception was antagonized by small doses (10-100 mu g) of the cannabinoid CB1 antagonist, SR141716A, applied in the tail. However, 100 mu g SR141716A injected subcutaneously in the back did not antagonize local Delta(9)-THC. Conclusions: These results indicate that the site of action of locally applied Delta(9)-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.