Proteinase activated receptor-4 signals pain in early but not late-stage post-traumatic osteoarthritis in rats

Abstract

Purpose: Serine proteinases such as thrombin and cathepsin-G are known to cleave and subsequently activate proteinase activated receptor-4 (PAR-4). In joints, selective peptide ligands that bind to PAR-4 cause sensitization of joint nociceptors and impart a marked pain response. Furthermore, blockade of PAR-4 with the antagonist pepducin p4Pal10 has been shown to reduce peripheral sensitization and joint pain, as well as ameliorating physiological signs of inflammation in an acute synovitis model.