Sex differences in cannabinoid antinociception against inflammatory pain

Abstract

We examined sex differences in antinociceptive and anti‐inflammatory effects of delta‐9‐tetrahydrocannabinol (THC) using the complete Freund's adjuvant (CFA) model of inflammatory pain (hindpaw CFA injection). Gonadally intact adult rats received THC systemically (0, 0.32, 10, 3.2 mg/kg i.p.) or intraplantar (0, 250, 500 μg i.pl.), on days 1, 3 and 7 post‐CFA. THC attenuated mechanical allodynia and thermal hyperalgesia in both sexes via both routes of administration, but tended to be more effective in females than males when given i.pl. THC also was more effective in females in reversing CFA‐suppressed drinking one day after CFA injection. In contrast, i.pl. THC decreased paw inflammation more in males. These results agree with previous studies demonstrating greater cannabinoid antinociception in females than males using acute pain models, and suggest that sex differences in the antinociceptive effects of THC in the CFA model are not related to its anti‐inflammatory properties. Additionally, i.pl. THC did not affect locomotor activity (or response latency in the uninflamed paw), indicating that greater antinociceptive effects of THC in females are not secondary to THC's greater sedative effect in females (observed when THC is given systemically). These results suggest that cannabinoids may be more effective analgesics in females than males. Supported by the State of Washington Initiative Measure No. 171.