Wasker Shimon Vinay Zedeck, Challoumas Dimitris, Weng Wai, Murrell George A C, Millar Neal L
Orthopaedic Research Institute, St George Hospital Sydney, University of New South Wales, Sydney, New South Wales, Australia.
School of Infection and Immunity, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
BMJ Open Sport Exerc Med. 2023 Feb 9;9(1):e001494. doi: 10.1136/bmjsem-2022-001494. eCollection 2023.
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.
神经源性疼痛和炎症被认为在肌腱病中起重要作用。本系统评价旨在呈现和评估肌腱病中神经源性炎症的证据。通过多个数据库进行系统检索，以识别通过相关细胞、受体、标志物和介质的上调来评估神经源性炎症的人类病例对照研究。使用一种新设计的工具对研究进行方法学质量评估。根据所评估的细胞/受体/标志物/介质汇总结果。共有31项病例对照研究符合纳入标准。肌腱病组织取自跟腱（n = 11）、髌腱（n = 8）、桡侧腕短伸肌肌腱（n = 4）、肩袖肌腱（n = 4）、肱二头肌远端肌腱（n = 3）和臀肌腱（n = 1）。通过基于所评估的神经源性炎症标志物汇总纳入研究的结果，我们发现与对照相比，肌腱病组织中蛋白基因产物9.5（PGP 9.5）、N-甲基-D-天冬氨酸受体、谷氨酸、谷氨酸受体（mGLUT）、神经肽Y（NPY）和肾上腺素能受体可能上调。未发现降钙素基因相关肽（CGRP）上调，并且其他几种标志物的证据相互矛盾。这些发现表明谷氨酰胺能和交感神经系统的参与以及神经长入标志物的上调，支持了神经源性炎症在肌腱病中起作用的概念。
