The present study is the first to investigate the participation of central
cyclooxygenase (COX) pathways in modulating the antinociceptive effects of intracisternally administered
cannabinoid on nociception induced by
inflammation of the temporomandibular joint (TMJ) in freely moving rats. Following
intra-articular injection of 5%
formalin in the TMJ, nociceptive scratching behavior was recorded for nine successive 5-min intervals in Sprague-Dawley rats. Intracisternal injection of 30 microg of
WIN 55,212-2, a synthetic non-subtype-selective CB1/2 agonist, administered 20 min prior to
formalin injection significantly reduced the number of scratches and duration of scratching induced by
formalin compared with the vehicle-treated group. Antinociceptive effect of
WIN 55,212-2 was blocked by intracisternal injection of 10 microg of
AM251, a
CB1 receptor-selective antagonist, but not by
AM630, a
CB2 receptor-selective antagonist.
A 10 microg dose of
WIN 55,212-2 that was ineffective in producing antinociception became effective following intracisternal administration of
NS-398, a selective
COX-2 inhibitor;
indomethacin, a non-selective COX 1/2 inhibitor;
acetaminophen, a putative COX-3 inhibitor, but not following pretreatment with the selective COX-1 inhibitor,
SC-560. The ED(50) value of
WIN 55,212-2 in the NS-398-treated group was significantly lower than that in the vehicle-treated group. Importantly, administration of low doses of COX inhibitors alone did not attenuate nociception. These results indicate that inhibition of central COX pathways, presumably via COX-2 inhibition, reduces inflammatory
pain by enhancing the
cannabinoid-induced antinociceptive effect. Based on our observations, combined administration of
cannabinoids with COX inhibitors may hold a therapeutic promise in the treatment of inflammatory TMJ
pain.