Proteinase‑Activated Receptors & Arthritis Pain

Protease Activated Receptor

During arthritis, proteases are released into the joint to cause tissue damage. These enzymes can also cleave a group of receptors called Protease Activated Receptors (PARs).

The McDougall Lab has identified PAR-2 and PAR-4 in joint tissues. Activation of these receptors sensitizes joint nerves leading to the generation of pain and inflammation. We have also found that selective antagonists can reduce pain and inflammation in models of rheumatoid arthritis and osteoarthritis.

Relevant Publications: 

Prophylactic inhibition of neutrophil elastase prevents the development of chronic neuropathic pain in osteoarthritic mice. MM Muley, E Krustev, AR Reid & JJ McDougall. Journal of Neuroinflammation. (2017)

Neutrophil Elastase-Induced Inflammation and Pain in Mouse Knee Joints via Activation of Proteinase Activated Receptor-2. MM Muley, AR Reid, B Botz, Z Helyes & JJ McDougall. British Journal of Pharmacology. (2016)

The Role of Proteases in Pain. JJ Mcougall & MM Muley. Handbook of Experimental Pharmacology. (2015)

Activation of PAR(2) receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint. FA Russell, N Schuelert, VE Veldhoen, MD Hollenberg & JJ McDougall. British Journal of Pharmacology. (2012)

The pronociceptive effect of proteinase-activated receptor-4 stimulation in rat knee joints is dependent on mast cell activation. FA Russell, S Zhan, A Dumas, S Lagarde, M Pouliot & JJ McDougall. Pain. (2011) 

Proteinase-Activated Receptor-4 (PAR(4)) Activation Leads to Sensitization of Rat Joint Primary Afferents Via a Bradykinin B-2 Receptor-Dependent Mechanism. FA Russell, VE Veldhoen, D Tchitchkan & JJ McDougall. Journal of Neurophysiology. (2010)

Involvement of transient receptor potential vanilloid 1 receptors in protease-activated receptor-2-induced joint inflammation and nociception.  Z Helyes, K Sandor, E Borbely, V Tekus, E Pinter, K Elekes, DM Toth, J Szolcsanyi & JJ McDougall. European Journal of Pain. (2010)

Triggering of Proteinase-Activated Receptor 4 Leads to Joint Pain and Inflammation in Mice. JJ Mcdougall, C Zhang, L Cellars, E Joubert, CM Dixon & N Vergnolle. Arthritis & Rheumatism. (2009)