Central cyclooxygenase inhibitors reduced IL-1β-induced hyperalgesia in temporomandibular joint of freely moving rats

Microinjection of formalin (5%, 50 μl) 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-1β-induced hyperalgesia with formalin-induced TMJ pain model. Intra-articular injection of 100 pg or 1 ng of IL-1β significantly facilitated formalin-induced behavior by 130 or 174% in the number of scratches. Intracisternal administration of 100 pg or 1 ng of IL-1β also significantly increased formalin-induced behavior by 166 or 82% in the number of scratches. IL-1β-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-1β-induced hyperalgesic response. Intracisternal pretreatment with NS-398, a selective COX-2 inhibitor, abolished the intracisternal administration of IL-1β-induced hyperalgesic response, while pretreatment with SC-560, a selective COX-1 inhibitor, did not change IL-1β-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-1β-induced hyperalgesic responses. These results indicate that central COX-2 plays important role in the central administration of IL-1β-induced hyperalgesia and that central COX-1/2 pathways mediate peripheral administration of IL-1β-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-1β-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.