title: The indirect antinociceptive mechanism of 15d-PGJ2 on rheumatoid arthritis-induced TMJ inflammatory pain in rats.
abstract: 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-Δ12,14-prostaglandin J2 (15d-PGJ2) 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)-α, interleukin (IL)-1β and keratinocyte-derived chemokine (KC) by enzyme-linked immunosorbent assay as well the expression of PKCε 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 μg/TMJ of mBSA after 24 h. Pretreatment with 15d-PGJ2 (30, 100 and 300 ng/TMJ) inhibited the RA-induced TMJ inflammatory hypernociception. In addition, 15d-PGJ2 reduced the RA-induced release of TNF-α, IL-1β and KC (p < 0.05) as well the expression of 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 hypernociception 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.
authors.affiliation: Laboratory of Biopathology and Molecular Biology, University of Uberaba, Brazil.
authors.forename: M S
authors.initials: MS
authors.lastname: Quinteiro
authors.forename: M H
authors.initials: MH
authors.lastname: Napimoga
authors.forename: K P
authors.initials: KP
authors.lastname: Mesquita
authors.forename: J-T
authors.initials: JT
authors.lastname: Clemente-Napimoga
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013705:Temporomandibular Joint Disorders / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C477819:15-deoxyprostaglandin J2; D000700:Analgesics; D018925:Chemokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C074302:keratinocyte-derived chemokines; D017868:Cyclic AMP-Dependent Protein Kinases; D051744:Protein Kinase C-epsilon; D015230:Prostaglandin D2