Alarmins in frozen shoulder: a molecular association between inflammation and pain

Cher, J. Z.B. et al. (2018) Alarmins in frozen shoulder: a molecular association between inflammation and pain. American Journal of Sports Medicine, 46(3), pp. 671-678. (doi: 10.1177/0363546517741127) (PMID:29190116)

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Background: The pathophysiological mechanisms behind proliferation of fibroblasts and deposition of dense collagen matrix in idiopathic frozen shoulder remain unclear. Alarmins (also known as danger signals) are endogenous molecules that are released into the extracellular milieu after infection or tissue injury and that signal cell and tissue damage. Purpose: To investigate whether the presence of alarmins is higher in patients with idiopathic frozen shoulder than in control subjects. Study Design: Controlled laboratory study. Methods: Shoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients with unstable shoulders (control). The samples were stained with hematoxylin and eosin (H&E) and analyzed by immunohistochemistry using antibodies against alarmin molecules including high-mobility group protein B1 (HMGB1), interleukin 33, S100A8, S100A9, and the peripheral nerve marker PGP9.5. Immunoreactivities were rated in a blinded fashion from “none” to “strong.” Immunohistochemical distribution within the capsule was noted. Before surgery, patient-ranked pain frequency, severity, stiffness, and the range of passive shoulder motion were recorded and statistically analyzed. Results: Compared with control patients, patients with frozen shoulder had greater frequency and severity of self-reported pain (P = .02) and more restricted range of motion in all planes (P < .05). H&E-stained capsular tissue from frozen shoulder showed fibroblastic hypercellularity and increased subsynovial vascularity. Immunoreactivity of alarmins was significantly stronger in frozen shoulder capsules compared with control capsules (P < .05). Furthermore, the expression of the alarmin molecule HMGB1 significantly correlated (r > 0.9, P < .05) with the severity of patient-reported pain. Conclusion: This study demonstrates a potential role for key molecular danger signals in frozen shoulder and suggests an association between the expression of danger molecules and the pain experienced by patients.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McLean, Michael and Millar, Professor Neal and Kitson, Miss Susan and Kerr, Mrs Shauna and Akbar, Mr Moeed and Crowe, Ms Lindsay and Garcia Melchor, Dr Emma
Authors: Cher, J. Z.B., Akbar, M., Kitson, S., Crowe, L. A.N., Garcia-Melchor, E., Hannah, S. C., McLean, M., Fazzi, U. G., Kerr, S. C., Murrell, G. A.C., and Millar, N. L.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:American Journal of Sports Medicine
ISSN (Online):1552-3365
Published Online:30 November 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in American Journal of Sports Medicine 46(3):671-678
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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