Tonic modulation of nociceptive behavior and allodynia by cannabinoid receptors in formalin test in rats.

Cannabinoids produce anti-nociceptive and anti-hyperalgesic effects in acute, inflammatory and neuropathic pain models. The current study investigated the role of cannabinoid (CB1 and CB2) receptors in modulating formalin-induced nociceptive behavior and mechanical allodynia in the rat. Rats received subcutaneous plantar injections of 5% formalin in the hind paws. Licking, biting and paw flinching nociceptive behaviors were measured 0-60 min after formalin injection. Allodynia was measured at 3 and 6 h, and 1, 3, 5 and 7 days post-injection using the mechanical paw withdrawal threshold. Animals in the experimental group were given i.p. injections of CB1 and CB2 receptor antagonists AM281 and AM630 at a dose of 1 mg/kg concomitant with formalin, and then twice daily for the following 7 days. AM281 and AM630 enhanced nociceptive behaviors, and attenuated the bilateral mechanical paw withdrawal threshold, compared with the vehicle. The results indicate that CB1 and CB2 receptors mediate a tonically inhibitory action on formalin-induced inflammatory pain, especially long-term allodynia, in bilateral hind paws.