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.
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.
Authors: Neal L Millar; Adam Meakins; Filip Struyf; Elaine Willmore; Abigail L Campbell; Paul D Kirwan; Moeed Akbar; Laura Moore; Jonathan C Ronquillo; George A C Murrell; Scott A Rodeo Journal: Nat Rev Dis Primers Date: 2022-09-08 Impact factor: 65.038
Authors: Moeed Akbar; Michael McLean; Emma Garcia-Melchor; Lindsay An Crowe; Paul McMillan; Umberto G Fazzi; David Martin; Angus Arthur; James H Reilly; Iain B McInnes; Neal L Millar Journal: PLoS One Date: 2019-04-23 Impact factor: 3.240
Authors: Lindsay A N Crowe; Michael McLean; Susan M Kitson; Emma Garcia Melchor; Katharina Patommel; Hai Man Cao; James H Reilly; William J Leach; Brain P Rooney; Simon J Spencer; Michael Mullen; Max Chambers; George A C Murrell; Iain B McInnes; Moeed Akbar; Neal L Millar Journal: Sci Rep Date: 2019-02-06 Impact factor: 4.379
Authors: Moeed Akbar; Lindsay A N Crowe; Michael McLean; Emma Garcia-Melchor; Lucy MacDonald; Kristyn Carter; Umberto G Fazzi; David Martin; Angus Arthur; James H Reilly; Iain B McInnes; Neal L Millar Journal: Proc Natl Acad Sci U S A Date: 2021-09-28 Impact factor: 11.205
Authors: Huan Yang; Qiong Zeng; Harold A Silverman; Manojkumar Gunasekaran; Sam J George; Alex Devarajan; Meghan E Addorisio; Jianhua Li; Téa Tsaava; Vivek Shah; Timothy R Billiar; Haichao Wang; Michael Brines; Ulf Andersson; Valentin A Pavlov; Eric H Chang; Sangeeta S Chavan; Kevin J Tracey Journal: Proc Natl Acad Sci U S A Date: 2021-08-17 Impact factor: 11.205