PAR(2) and temporomandibular joint inflammation in the rat.
The proteinase-activated receptor 2 (PAR(2)) is a putative therapeutic target for arthritis. We hypothesized that the early pro-inflammatory effects secondary to its activation in the temporomandibular joint (TMJ) are mediated by neurogenic mechanisms. Immunofluorescence analysis revealed a high degree of neurons expressing PAR(2) in retrogradely labeled trigeminal ganglion neurons. Furthermore, PAR(2) immunoreactivity was observed in the lining layer of the TMJ, co-localizing with the neuronal marker PGP9.5 and substance-P-containing peripheral sensory nerve fibers. The intra-articular injection of PAR(2) agonists into the TMJ triggered a dose-dependent increase in plasma extravasation, neutrophil influx, and induction of mechanical allodynia. The pharmacological blockade of natural killer 1 (NK(1)) receptors abolished PAR(2)-induced plasma extravasation and inhibited neutrophil influx and mechanical allodynia. We conclude that PAR(2) activation is pro-inflammatory in the TMJ, through a neurogenic mechanism involving NK(1) receptors. This suggests that PAR(2) is an important component of innate neuro-immune response in the rat TMJ.
Denadai-Souza
A
A
Dept. of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, 05508-900 SP, Brazil.
Cenac
N
N
Casatti
C A
CA
Câmara
P R de Souza
PR
Yshii
L M
LM
Costa
S K P
SK
Vergnolle
N
N
Muscará
M N
MN
D000818:Animals; D001168:Arthritis / Q000473:pathology*; D001177:Arthropathy, Neurogenic / Q000473:pathology; D007113:Immunity, Innate / Q000276:immunology; D007270:Injections, Intra-Articular; D008297:Male; D009412:Nerve Fibers / Q000473:pathology; D015213:Neuroimmunomodulation / Q000276:immunology; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000473:pathology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010147:Pain Measurement; D010880:Piperidines / Q000494:pharmacology; D010949:Plasma; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000819:agonists / Q000032:analysis*; D011984:Sensory Receptor Cells / Q000473:pathology; D013373:Substance P / Q000032:analysis; D013704:Temporomandibular Joint / Q000294:innervation; D013705:Temporomandibular Joint Disorders / Q000473:pathology*; D012668:Trigeminal Ganglion / Q000473:pathology; D014357:Trypsin / Q000008:administration & dosage / Q000494:pharmacology; D043222:Ubiquitin Thiolesterase / Q000032:analysis
D064729:Neurokinin-1 Receptor Antagonists; D009842:Oligopeptides; D010880:Piperidines; D011812:Quinuclidines; D044464:Receptor, PAR-2; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; C085215:SR 140333; D013373:Substance P; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; D014357:Trypsin