title: Posttraumatic elbow contractures: targeting neuroinflammatory fibrogenic mechanisms.
abstract: Posttraumatic elbow stiffness remains a common and challenging clinical problem. In the setting of a congruent articular surface, the joint capsule is regarded as the major motion-limiting anatomic structure. The affected joint capsule is characterized by irreversible biomechanical and biochemical fibrogenic changes strikingly similar to those observed in many other fibroproliferative human conditions. Studies in humans and preclinical animal models are providing emergent evidence that neuroinflammatory mechanisms are critical upstream events in the pathogenesis of posttraumatic connective tissue fibrogenesis. Maladaptive recruitment and activation of mast cell infiltrates coupled with the aberrant expression of growth factors such as transforming growth factor-beta, nerve growth factor, and neuropeptides such as substance P are common observations in posttraumatic joint contractures and many other fibroproliferative disorders. Blockade of these factors is providing promising evidence that if treatment is timed correctly, the fibrogenic process can be interrupted or impeded. This review serves to highlight opportunities derived from these recent discoveries across many aberrant fibrogenic disorders as we strive to develop novel, targeted antifibrotic prevention and treatment strategies for posttraumatic elbow stiffness.
authors.affiliation: Department of Orthopaedic Surgery, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Rm #4260, Salt Lake City, UT, 84112, USA, michael.monument@hci.utah.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Monument
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
authors.forename: Paul T
authors.initials: PT
authors.lastname: Salo
authors.forename: A Dean
authors.initials: AD
authors.lastname: Befus
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Hildebrand
mesh_terms: D000818:Animals; D003286:Contracture / Q000473:pathology* / Q000503:physiopathology; D004551:Elbow Joint / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005353:Fibronectins / Q000032:analysis; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D017746:Joint Capsule / Q000378:metabolism / Q000473:pathology*; D008297:Male; D016059:Range of Motion, Articular / Q000502:physiology; D000092464:Elbow Injuries
chemical_list: D005353:Fibronectins; D018836:Inflammation Mediators