Blockade of central cyclooxygenase (COX) pathways enhances the cannabinoid-induced antinociceptive effects on inflammatory temporomandibular joint (TMJ) nociception.
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.
Ahn
Dong K
DK
Department of Oral Physiology and BrainKorea21, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea. dkahn@knu.ac.kr
Choi
Hyo S
HS
Yeo
Sang P
SP
Woo
Young W
YW
Lee
Min K
MK
Yang
Gwi Y
GY
Jeon
Hye J
HJ
Park
Jae S
JS
Mokha
Sukhbir S
SS
D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D001168:Arthritis / Q000188:drug therapy* / Q000503:physiopathology*; D002186:Cannabinoids / Q000008:administration & dosage*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013706:Temporomandibular Joint Dysfunction Syndrome / Q000188:drug therapy* / Q000503:physiopathology*
D000700:Analgesics; D002186:Cannabinoids; D011451:Prostaglandin-Endoperoxide Synthases