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

Abstract

  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 Δ⁹-tetrahydrocannabinol (Δ⁹-THC) can attenuate capsaicin-induced nociception in rhesus monkeys. Methods: Capsaicin (100 µg) was applied locally in the tail of rhesus monkeys to evoke a nociceptive response, thermal allodynia, in normally innocuous 46°C water. Δ⁹-THC (10–320 µg) 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 Δ⁹-THC action. Results:Δ⁹-THC dose-dependently inhibited capsaicin-induced allodynia. This local antinociception was antagonized by small doses (10–100 µg) of the cannabinoid CB₁ antagonist, SR141716A, applied in the tail. However, 100 µg SR141716A injected subcutaneously in the back did not antagonize local Δ⁹-THC. Conclusions: These results indicate that the site of action of locally applied Δ⁹-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.