Enhanced expression of neuronal proteins in idiopathic frozen shoulder

Background: Our understanding of the pathogenesis of frozen shoulder and why it is so painful is undetermined. This study investigated the expression of neuronal proteins in the capsular tissue of frozen shoulder. Methods: Shoulder capsular samples were collected from 8 patients with idiopathic adhesive capsulitis and 10 patients with a rotator cuff tear but no stiffness (controls). Samples were analyzed by immunohistochemistry using antibodies against protein gene product 9.5 (PGP9.5), a general nerve marker; growth associated protein 43 (GAP43), a nerve growth marker; nerve growth factor receptor p75; and CD34, an endothelial cell marker. Results: Samples from frozen shoulders showed subsynovial hypercellularity and fibroblastic proliferation, with increased expression of nerve growth factor receptor p75 and CD34 compared with controls. Nerves positive for PGP9.5 and GAP43 were more abundant in samples of frozen shoulder (2.8 +/- 0.2 and 2.4 +/- 0.4 per field; P < .01) compared with controls (1.6 +/- 0.3 and 1.3 +/- 0.3 per field; P < .05). Expression of neuronal proteins followed that of CD34. Conclusion: Increased expression of nerve growth factor receptor and new nerve fibers were found in the shoulder capsular tissue of patients with frozen shoulder compared with those without a frozen shoulder. These data suggest that neoinnervation and neoangiogenesis in the shoulder capsule are important events in the pathogenesis of frozen shoulder and may help explain the often-severe pain of patients with frozen shoulder.