Enhanced expression of neuronal proteins in idiopathic frozen shoulder
Xu Y, Bonar F, Murrell GA.  J Shoulder Elbow Surg. 2011 Oct 15. [Epub ahead of print]
Idiopathic frozen shoulder (adhesive capsulitis) is a mysterious and misunderstood injury.  It is characterized by decreases in both active and passive shoulder range of motion in addition to severe pain without any known origin.  Recent research has found increased protein expression of growth factors and inflammatory mediators as well as increased nerve cells in the joint capsule.  However these studies lacked a control group.  Therefore, Xu et al. examined the protein expression of nerve cells in the capsule of patients with idiopathic frozen shoulder compared to patients without. Shoulder capsule tissue was collected during arthroscopic capsular release (idiopathic frozen shoulder group, n = 8) and rotator cuff surgery (control group, n = 10).  These tissue samples were taken from the capsule just superior to the subscapularis and lateral to the glenoid labrum.  Standard immunohistochemistry procedures (methods to detect proteins in tissues with microscopes) were performed to examine the tissue for nerve growth factor receptors as well as markers of blood vessels, nerves, and nerve growth factors.  Staining of the tissues was performed to examine the distribution of cells.  The capsule was divided into synovial and capsule tissue for analysis.  They found that the capsule tissue of frozen shoulder patients had hypercellularity (increased density of cells) and fibroblastic proliferation (associated with fibrosis) compared to controls.  They also found that frozen shoulder patients had increased expression of nerve growth factor receptors as well as markers of blood vessels, nerves, and nerve growth factors compared to controls. 
This study is a large step in understanding the pathogenesis of idiopathic frozen shoulder.  The results indicate that patients with idiopathic frozen shoulder have increased expression of several nerve and vascular proteins, which also correspond to tissue fibrosis.  The increased nerve growth explains why frozen shoulder is very painful and the presence of vascular proteins suggests that an inflammatory response can very easily occur if the healthcare provider is too aggressive with joint mobilizations or range of motion exercises.  If this occurs the overloading can easily trigger a cascade of biologic events that causes more pain and further decreases in shoulder range of motion due to tissue fibrous.  This often occurs when working with patients with frozen shoulder and is often difficult to avoid.  This demonstrates the challenges facing frozen shoulder and the delicate balance between “not enough” and “too much” mobilization.  This study can help clinicians design better rehabilitation strategies to treat and manage these patients with the use of medications and less aggressive exercises.  However, it still does not fully capture the pathogenesis of frozen shoulder.  Studies are warranted in patients at high risk to understand why and how this condition develops.  Longitudinal studies are almost impossible and therefore cross-sectional studies in high-risk populations (diabetic patients) or animal studies may determine if native tissue properties are altered.  These altered tissue properties may be the catalyst to the development of frozen shoulder.  What is your experience with frozen shoulder?  Do these results help support what you see clinically?  What is your rehabilitation approach with these patients?
Written by:  Stephen Thomas
Reviewed by:  Jeffrey Driban

Xu Y, Bonar F, & Murrell GA (2011). Enhanced expression of neuronal proteins in idiopathic frozen shoulder. Journal of Shoulder and Elbow Surgery PMID: 22005128