TRPV4 and TRPM8 as putative targets for chronic low back pain alleviation

Stefania Fozzato,Nicolò Baranzini,Raffaella Cinquetti,Michele Francesco Surace,Elena Bossi,Paola Campomenosi,Annalisa Grimaldi

doi:10.1007/s00424-020-02460-8

Abstract

The purpose of this study is to investigate the presence of nervous fibers and expression of TRP channels in samples harvested during decompressive/fusion spine surgeries from patients affected by chronic low back pain (CLBP). The aim was to understand if members of this family of receptors played a role in detection and processing of painful stimuli, to eventually define them as potential targets for CLBP alleviation. Expression of transient receptor potential (TRP) channels (A1, V1, V2, V4, and M8) was evaluated in samples from different periarticular sites of 6 patients affected by CLBP, at both protein and transcript levels. The capsular connective pathological tissue appeared infiltrated by sensitive unmyelinated nervous fibers. An increase in TRP channel mRNAs and proteins was observed in the pathological capsule compared with tissues collected from the non-symptomatic area in five of the six analyzed patients, independently by the location and number of affected sites. In particular, TRPV4 and TRPM8 were consistently upregulated in pathological tissues. Interestingly, the only patient showing a different pattern of expression also had a different clinical history. TRPV4 and TRPM8 channels may play a role in CLBP and warrant further investigations as possible therapeutic targets.

Highlights

Chronic low back pain (CLBP) is a painful condition arising from spinal structures such as bones, joints, muscles, tendons, Paola Campomenosi and Michele Francesco Surace share last authorship
In order to shed light on the role played by different transient receptor potential (TRP) channels in the detection and processing of painful stimuli, and possibly to identify novel therapeutic targets, we investigated their expression in samples from patients affected by CLBP surgically treated
Hematoxylin and eosin (Fig. 1a–n) and Masson Trichrome (Fig. 1a′–n′) stains were performed to evaluate any gross morphological changes in the joint tissues deriving from the painaffected sites compared with control ones

Summary

Introduction

Chronic low back pain (CLBP) is a painful condition arising from spinal structures such as bones, joints, muscles, tendons, Paola Campomenosi and Michele Francesco Surace share last authorship. CLBP is a highly prevalent condition associated with disability, work absenteeism, and huge healthcare costs [36]. The inflammatory response prompts the release of an array of molecules that acts in altering the expression and modulating the function of various ion channels as the transient receptor potential (TRP) ion channels, sodium channels, and mechanosensitive ion channels in nociceptors inducing sensitization, pain hypersensitivity, or hyperalgesia [7, 35]. TRP channels are sensitized, their activation threshold reduced, and, perception of painful (hyperalgesia) and non-painful (allodynia) stimuli enhanced [19, 21, 25]

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