Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Background: Inflammation of the temporomandibular joint (TMJ) induced by rheumatoid arthritis (RA) have 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 15-deoxy-(Delta 12,14)-prostaglandin J(2) (15d-PGJ(2)) into TMJ has a potential peripheral antinociceptive effect, the aim of this study was to evaluate the peripheral effect of 15d-PGJ2 in RA-induced TMJ inflammatory hypernociception. Methods: Antigen-induced arthritis (AIA) was generated in rats with methylated bovine serum albumin (mBSA). RA-induced TMJ hypernociception was assessed by measuring the behavioural nociceptive responses. After behavioural experiments, the animals were terminally anaesthetized and periarticular tissues were removed and homogenized. The supernatants were used to evaluate the levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and keratinocyte-derived chemokine (KC) by enzyme-linked immunosorbent assay as well the expression of PKC epsilon and PKA by western blotting analysis. Results: The intra-articular injection of mBSA, but not phosphate buffered saline (control), in immunized rats induced dose-and time-dependent behavioural nociceptive responses in which the peak of nociceptive responses were obtained by using 10 mu g/TMJ of mBSA after 24 h. Pretreatment with 15d-PGJ(2) (30, 100 and 300 ng/TMJ) inhibited the RA-induced TMJ inflammatory hypernociception. In addition, 15d-PGJ(2) reduced the RA-induced release of TNF-alpha, IL-1 beta and KC (p < 0.05) as well the expression of PKA and PKC epsilon (p < 0.05). Conclusions: In the present study, we demonstrated that 15d-PGJ(2) was able to reduce the RA-induced TMJ inflammatory hypernociception by an indirect mechanism. This antinociceptive effect is in part due to decrease of TNF-alpha, IL-1 beta and KC levels and PKA/PKC epsilon expression in the TMJ.16811061115Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2011/00683-5]Fundacao de Amparo a Pesquisa do Estado de Minas Gerais, Brazil [FAPEMIG PPM 097/09]