Central cyclooxygenase inhibitors reduced IL-1beta-induced hyperalgesia in temporomandibular joint of freely moving rats.
Microinjection of formalin (5%, 50 microl) into a temporomandibular joint (TMJ) causes noxious behavioral responses in freely moving rats. In the present study, we investigated the role of central cyclooxygenase (COX) pathways in IL-1beta-induced hyperalgesia with formalin-induced TMJ pain model. Intra-articular injection of 100 pg or 1 ng of IL-1beta significantly facilitated formalin-induced behavior by 130 or 174% in the number of scratches. Intracisternal administration of 100 pg or 1 ng of IL-1beta also significantly increased formalin-induced behavior by 166 or 82% in the number of scratches. IL-1beta-induced hyperalgesia was blocked by pretreatment with IL-1 receptor antagonist. Intracisternal pretreatment with SC-560, a selective COX-1 inhibitor, or NS-398, a selective COX-2 inhibitor, abolished intra-articular administration of IL-1beta-induced hyperalgesic response. Intracisternal pretreatment with NS-398, a selective COX-2 inhibitor, abolished the intracisternal administration of IL-1beta-induced hyperalgesic response, while pretreatment with SC-560, a selective COX-1 inhibitor, did not change IL-1beta-induced hyperalgesic responses. On the other hand, pretreatment with acetaminophen, a tentative COX-3 inhibitor, also abolished both intra-articular and intracisternal administration of IL-1beta-induced hyperalgesic responses. These results indicate that central COX-2 plays important role in the central administration of IL-1beta-induced hyperalgesia and that central COX-1/2 pathways mediate peripheral administration of IL-1beta-induced hyperalgesia in the TMJ. Central COX-3 inhibitor seems to play an important role in the nociceptive process associated with both peripheral and central administration of IL-1beta-induced hyperalgesia in TMJ. It is concluded that central acting of COX-3 inhibitors may be of therapeutic value in the treatment of inflammatory pain in TMJ.
Ahn
Dong K
DK
Department of Oral Physiology, School of Dentistry, Kyungpook National University, 188-1 Sam Deok 2 ga, Chung-gu, Daegu 700-412, South Korea. dkahn@knu.ac.kr
Chae
Jong M
JM
Choi
Hyo S
HS
Kyung
Hee M
HM
Kwon
Oh W
OW
Park
Hyo S
HS
Youn
Dong H
DH
Bae
Yong C
YC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D005070:Evans Blue; D005557:Formaldehyde; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007375:Interleukin-1; D008297:Male; D009578:Nitrobenzenes / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage*; D013705:Temporomandibular Joint Disorders / Q000139:chemically induced / Q000503:physiopathology*; D013997:Time Factors; D014851:Wakefulness
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D009578:Nitrobenzenes; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D005557:Formaldehyde; D005070:Evans Blue