IMR Press / FBL / Volume 19 / Issue 8 / DOI: 10.2741/4280

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
Neuronal pathways in tendon healing and tendinopathy--update
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1 Integrative Orthopaedic Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
2 Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford UK
3 McCaig Institute for Bone and Joint Health, Department of Surgery, University of Calgary, Calgary, Alberta, Canada
Front. Biosci. (Landmark Ed) 2014, 19(8), 1251–1278; https://doi.org/10.2741/4280
Published: 1 June 2014
Abstract

The regulatory mechanisms involved in tendon homeostasis and repair are not fully understood. Accumulating data, however, demonstrate that the nervous system, in addition to afferent (sensory) functions, through efferent pathways plays an active role in regulating pain, inflammation, and tissue repair. In normal-, healing- and tendinopathic tendons three neurosignalling pathways consisting of autonomic, sensory and glutamatergic neuromediators have been established. In healthy tendons, neuromediators are found in the paratenon, whereas the proper tendon is practically devoid of nerves, reflecting that normal tendon homeostasis is regulated by pro- and anti-inflammatory mediators from the tendon surroundings. During tendon repair, however, there is extensive nerve ingrowth into the tendon proper and subsequent time-dependent appearance of sensory, autonomic and glutamatergic mediators, which amplify and fine-tune inflammation and tendon regeneration. In tendinopathy, excessive and protracted sensory and glutamatergic signalling may be involved in inflammatory, painful and hypertrophic tissue reactions. As our understanding of these processes improves, neuronal mediators may prove to be useful in the development of targeted pharmacotherapy and tissue engineering approaches to painful, degenerative and traumatic tendon disorders.

Keywords
Neurotransmitters
Neuropeptides
Glutamate
Opioids
Tendon
Healing
Pain
Tendinopathy
Review
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