The most common histological finding in carpal tunnel syndrome (CTS) is non-inflammatory fibrosis and thickening of the subsynovial connective tissue (SSCT) in the tunnel. were less in the control SSCT fibroblasts than in the fibroblasts from rabbits with surgical interventions. The surgical interventions did not result in any alteration of collagen III expression. However, both surgical interventions resulted in a significant decrease in collagen VI expression compared to the control group. The two surgical interventions PIK3C2G achieved comparable expression of TGF- receptors and collagens. Our results provide evidence that this SSCT is sensitive to surgical interventions, even when these are modest. Since SSCT fibrosis is usually a hallmark of carpal tunnel syndrome, these data also suggest that such fibrosis could result from relatively minor trauma. Keywords: Carpal Tunnel Syndrome, Subsynovial Connective Tissue INTRODUCTION Carpal tunnel syndrome (CTS) is the most common compression neuropathy, but in most cases the etiology is usually idiopathic.1,2 The compression can result from a reduction in size of the carpal tunnel or an increase in the volume of its contents. The most common pathological findings significantly favor the latter.3C8 The subsynovial connective tissue (SSCT) has a unique structure in the carpal tunnel,8C11 loosely connecting the median nerve, flexor tendons, and visceral synovium of the ulnar bursa. Non-inflammatory fibrosis and thickening of the SSCT are commonly recognized in CTS patients.3C8,12 While the cause of SSCT fibrosis and its relationship to CTS are unknown, one hypothesis is that SSCT injury causes fibrosis, and that the fibrosis then prospects to CTS. Salirasib To better understand the role of SSCT fibrosis as an etiologic factor for CTS, a rabbit model was developed.13 In this model, a shear injury of the SSCT is created by surgically stretching the SSCT beyond its elastic limit.14 Rabbits with this injury developed median neuropathy, similar to that seen in human CTS.15 We investigated the effects of this surgical intervention on the synthesis of TGF- receptors, and collagens III and VI in the SSCT in this model in comparison to a sham procedure, in which the skin was incised but neither the tendon nor SSCT were injured. We hypothesized that this expression of TGF- receptors and collagen would be affected by the SSCT shear injury, but not by the skin incision. METHODS Animals The experimental protocol was approved by our Institutional Animal Care and Use Committee. 18 New Zealand white rabbits weighing 3.6 to 4.2 kg were used. The rabbits were Salirasib evenly divided into 2 groups for either skin incision alone or skin incision with tendon laceration and SSCT stretching.13 Nine other rabbits, without any intervention at their wrists, were obtained from other studies in our institution to serve as a normal control group. Surgical Interventions Following the induction of anesthesia, both forepaws were scrubbed with povidone-iodine and sterilely draped. A rubber belt was used above the elbow as a tourniquet. For the skin incision with tendon laceration and SSCT stretching intervention (SSCT shear), a volar longitudinal incision (12 mm long) was centered 1 cm proximal to the proximal edge of the Salirasib wrist cartilage of one randomly selected forepaw, and the flexor digitorum superficialis (FDS) tendon of the middle digit was uncovered. After identifying the level of the muscle-tendon junction of the middle digit FDS and marking the flexor carpi ulnaris (FCU) tendon using a 6-0 Prolene (Ethicon, Somerville, NJ) suture to identify the relative position of the middle digit FDS tendon, the middle digit FDS tendon was cut at the muscle-tendon junction, and the distal end of the middle digit FDS was also marked using 6-0 Prolene. Then, a volar longitudinal incision (11 mm long) was made on the 3rd digit centered at the metacarpophalangeal joint level to expose the flexor tendons and proximal annular pulley. Two marks separated by 5 mm were made on the surface of the middle digit FDS tendon in this 2nd incision. Then the 2 tendon marks were approximated and sutured together using 5-0 Ethibond (Ethicon, Somerville, NJ). Thus, the middle digit FDS tendon was distally shifted.