Is neurogenic inflammation involved in tendinopathy? A systematic review

Wasker, S. V. Z., Challoumas, D., Weng, W., Murrell, G. A.C. and Millar, N. L. (2023) Is neurogenic inflammation involved in tendinopathy? A systematic review. BMJ Open Sport and Exercise Medicine, 9(1), e001494. (doi: 10.1136/bmjsem-2022-001494) (PMID:36793930) (PMCID:PMC9923261)

Abstract

Neurogenic pain and inflammation have been hypothesised to play an important role in tendinopathy. This systematic review aimed to present and assess the evidence on neurogenic inflammation in tendinopathy. A systematic search was conducted through multiple databases to identify human case–control studies assessing neurogenic inflammation through the upregulation of relevant cells, receptors, markers and mediators. A newly devised tool was used for the methodological quality assessment of studies. Results were pooled based on the cell/receptor/marker/mediator assessed. A total of 31 case–control studies were eligible for inclusion. The tendinopathic tissue was obtained from Achilles (n=11), patellar (n=8), extensor carpi radialis brevis (n=4), rotator cuff (n=4), distal biceps (n=3) and gluteal (n=1) tendons. Through pooling the results of included studies based on the marker of neurogenic inflammation assessed, we identified possible upregulation of protein gene product 9.5 (PGP 9.5), N-methyl-D-aspartate Receptors, glutamate, glutamate receptors (mGLUT), neuropeptide Y (NPY) and adrenoreceptors in tendinopathic tissue versus control. Calcitonin gene-related peptide (CGRP) was not found to be upregulated, and the evidence was conflicting for several other markers. These findings show the involvement of the glutaminergic and sympathetic nervous systems and the upregulation of nerve ingrowth markers supporting the concept that neurogenic inflammation plays a role in tendinopathy.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Challoumas, Mr Dimitris and Millar, Professor Neal
• Authors: Wasker, S. V. Z., Challoumas, D., Weng, W., Murrell, G. A.C., and Millar, N. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: BMJ Open Sport and Exercise Medicine
• Publisher: BMJ Publishing Group
• ISSN: 2055-7647
• ISSN (Online): 2055-7647
• Published Online: 09 February 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in BMJ Open Sport and Exercise Medicine 9(1): e001494
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
301515		Damage mechanisms in tendon disease	Neal Millar	Medical Research Council (MRC)	MR/R020515/1	III - Immunology