Systemic Desensitization Through TRPA1 Channels by Capsazepine and Mustard Oil - a Novel Strategy Against Inflammation and Pain

Overview

Journal Sci Rep

Specialty Science

Date 2016 Jul 1

PMID 27356469

Citations 48

Authors

Katrin Kistner

Norbert Siklosi

Alexandru Babes

Mohammad Khalil

Tudor Selescu

Katharina Zimmermann

Stefan Wirtz

Christoph Becker

Markus F Neurath

Peter W Reeh

Matthias A Engel

Affiliations

Soon will be listed here.

Abstract

We demonstrate a novel dual strategy against inflammation and pain through body-wide desensitization of nociceptors via TRPA1. Attenuation of experimental colitis by capsazepine (CPZ) has long been attributed to its antagonistic action on TRPV1 and associated inhibition of neurogenic inflammation. In contrast, we found that CPZ exerts its anti-inflammatory effects via profound desensitization of TRPA1. Micromolar CPZ induced calcium influx in isolated dorsal root ganglion (DRG) neurons from wild-type (WT) but not TRPA1-deficient mice. CPZ-induced calcium transients in human TRPA1-expressing HEK293t cells were blocked by the selective TRPA1 antagonists HC 030031 and A967079 and involved three cysteine residues in the N-terminal domain. Intriguingly, both colonic enemas and drinking water with CPZ led to profound systemic hypoalgesia in WT and TRPV1(-/-) but not TRPA1(-/-) mice. These findings may guide the development of a novel class of disease-modifying drugs with anti-inflammatory and anti-nociceptive effects.

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