Methods: Antigen-induced arthritis (AIA) was generated in rats with methylated bovine serum albumin (mBSA). RA-induced TMJ hyperalgesia was assessed by measuring the behavioral nociceptive responses, such as rubbing the orofacial region and flinching the head , induced by the injection of low dose of formalin (0.5%) into TMJ prior challenge with an intra-articular injection of mBSA. After behavioral experiments, animals were terminally anesthetized and periarticular tissues were removed and homogenized. The supernatants were used to evaluate the levels of TNF-α, IL-1β and KC by ELISA as well the expression of PKCε and PKA by Western blot analysis.
Results: The intraarticular injection of mBSA, but not PBS (control), in immunized rats induced dose- and time-dependent behavioral nociceptive responses in which the peak of behavioral nociceptive responses were obtained by using 10 ug/TMJ of mBSA after 24 h. Pretreatment (15 min) with 15d-PGJ2 (30, 100 and 300 ng/TMJ) inhibited the RA-induced TMJ inflammatory hyperalgesia. In addition, 15d-PGJ2 reduced the RA-induced release of TNF-α, IL-1β and KC (p<0.05) as well the expression of proteinkinases PKA and PKCε (p<0.05).
Conclusions: In the present study, we demonstrated that 15d-PGJ2 was able to reduce the RA-induced TMJ inflammatory hyperalgesia by an indirect mechanism. This antinociceptive effect is in part due to decrease of TNF-α, IL-1β and KC levels and PKA/PKCε expression in the TMJ.