Capsaicin-sensitive sensory nerves, TRPV1 receptors and tachykinins play important roles in mast cell tryptase-induced arthritis and hyperalgesia

Zsuzsanna Helyes,Jason J Mcdougall,Éva Borbély,Adrienn Markovics,John P Quinn,János Szolcsányi,Katalin Sándor,Erika Pintér

doi:10.1186/1471-2210-11-s2-a50

Abstract

Background Protease-activated receptors (PARs) are G protein-coupled receptors activated through proteolytic cleavage. They are localized on epithelial, endothelial and inflammatory cells, as well as on Transient Receptor Potential Vanilloid 1 (TRPV1) receptor-expressing capsaicin-sensitive sensory nerves. Tachykinins, such as substance P (SP) and neurokinin A (NKA) encoded by the TAC1 gene are released from these fibres and play an important role in inflammatory and nociceptive processes. We investigated the involvement of capsaicin-sensitive peptidergic afferents, TRPV1 ion channels and TAC1-encoded tachykinins in mast cell tryptase (MCT)-induced joint swelling, hyperalgesia and synovial microcirculation.

Highlights

Protease-activated receptors (PARs) are G protein-coupled receptors activated through proteolytic cleavage
We investigated the involvement of capsaicin-sensitive peptidergic afferents, Transient Receptor Potential Vanilloid 1 (TRPV1) ion channels and TAC1-encoded tachykinins in mast cell tryptase (MCT)-induced joint swelling, hyperalgesia and synovial microcirculation
MCT-induced joint swelling and secondary hyperalgesia were significantly reduced in TAC1−/− and neurokinin 1 receptor (NK1)−/− mice, but not in the other groups compared to WTs

Summary

Introduction

Protease-activated receptors (PARs) are G protein-coupled receptors activated through proteolytic cleavage. They are localized on epithelial, endothelial and inflammatory cells, as well as on Transient Receptor Potential Vanilloid 1 (TRPV1) receptor-expressing capsaicin-sensitive sensory nerves. Tachykinins, such as substance P (SP) and neurokinin A (NKA) encoded by the TAC1 gene are released from these fibres and play an important role in inflammatory and nociceptive processes. We investigated the involvement of capsaicin-sensitive peptidergic afferents, TRPV1 ion channels and TAC1-encoded tachykinins in mast cell tryptase (MCT)-induced joint swelling, hyperalgesia and synovial microcirculation

Methods

Results

Conclusion