Local administration of delta9-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 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.

Fig. 1

Local antinociceptive effects of Δ⁹-THC administered in the tail (hashed bars) or in the back (filled bars) against 46°C water in the presence of capsaicin (100 µg) or 50°C water in the absence of capsaicin. Each value represents the mean±SEM (n=4). Asterisks represent a significant difference (**P<0.01) from control. Abscissa: Δ⁹-THC local doses in µg. Ordinate: percent of maximum possible effect (%MPE). Each data point was obtained 15 min after injection. See Materials and methods for other details

Fig. 2

Local antagonist effects of SR141716A administered in the tail (hashed bars) and in the back (filled bars) against local Δ⁹-THC in 46°C water in the presence of capsaicin. VEH represents the vehicle effect in the condition of coadministration of 100 µg capsaicin and 320 µg Δ⁹-THC in the tail. Other details as in Fig. 1