PT  - JOURNAL ARTICLE
AU  - Shimon Vinay Zedeck Wasker
AU  - Dimitris Challoumas
AU  - Wai Weng
AU  - George A C Murrell
AU  - Neal L Millar
TI  - Is neurogenic inflammation involved in tendinopathy? A systematic review
AID  - 10.1136/bmjsem-2022-001494
DP  - 2023 Feb 01
TA  - BMJ Open Sport & Exercise Medicine
PG  - e001494
VI  - 9
IP  - 1
4099  - http://bmjopensem.bmj.com/content/9/1/e001494.short
4100  - http://bmjopensem.bmj.com/content/9/1/e001494.full
SO  - BMJ OPEN SP EX MED2023 Feb 01; 9
AB  - 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.