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.