RT Journal Article SR Electronic T1 Is neurogenic inflammation involved in tendinopathy? A systematic review JF BMJ Open Sport & Exercise Medicine JO BMJ OPEN SP EX MED FD BMJ Publishing Group Ltd SP e001494 DO 10.1136/bmjsem-2022-001494 VO 9 IS 1 A1 Shimon Vinay Zedeck Wasker A1 Dimitris Challoumas A1 Wai Weng A1 George A C Murrell A1 Neal L Millar YR 2023 UL http://bmjopensem.bmj.com/content/9/1/e001494.abstract 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.