The indirect antinociceptive mechanism of 15d-PGJ2 on RA-induced TMJ hyperalgesia

Objectives: Inflammation of the temporomandibular joint (TMJ) induced by Rheumatoid Arthritis (RA) have often resulted in persistent pain and caused distress to many patients. Considering that not all patients respond to traditional drugs therapy to RA and it has demonstrated that 15d-PGJ2 into the TMJ has a potential antinociceptive effect, the aim of this study was to evaluate the peripheral effect of 15d-PGJ₂ in RA-induced TMJ inflammatory hyperalgesia in rats as well its mechanisms.

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.