Carpal Tunnel Syndrome Pathophysiology: Role of Subsynovial Connective Tissue

Abstract

Carpal tunnel syndrome (CTS) is a very common pathology. Its most common diagnosis is idiopathic. Although it is accepted that chronic increase in pressure within the carpal tunnel is responsible for median nerve neuropathy, the exact pathophysiology leading to this pressure increase remains unknown. All the histological studies of the carpal tunnel in the CTS find a noninflammatory thickening of the subsynovial connective tissue (SSCT), which seems to be a characteristic of this pathology. Numerous animal models have been developed to recreate CTS in vivo to develop and improve preventive strategies and effective conservative treatments by a better understanding of its pathophysiology. The creation of a shear injury of the SSCT in a rabbit model induced similar modifications to what is observed in CTS, suggesting that this could be a pathway leading to idiopathic CTS.

Keywords

carpal tunnel - subsynovial connective tissue - animal models

• References

• 1 Katz JN, Simmons BP. Clinical practice. Carpal tunnel syndrome. N Engl J Med 2002; 346 (23) 1807-1812
• 2 Tanaka S, Wild DK, Seligman PJ, Behrens V, Cameron L, Putz-Anderson V. The US prevalence of self-reported carpal tunnel syndrome: 1988 National Health Interview Survey data. Am J Public Health 1994; 84 (11) 1846-1848
• 3 de Krom MC, Kester AD, Knipschild PG, Spaans F. Risk factors for carpal tunnel syndrome. Am J Epidemiol 1990; 132 (6) 1102-1110
• 4 Gelberman RH, Rydevik BL, Pess GM, Szabo RM, Lundborg G. Carpal tunnel syndrome. A scientific basis for clinical care. Orthop Clin North Am 1988; 19 (1) 115-124
• 5 Diao E, Shao F, Liebenberg E, Rempel D, Lotz JC. Carpal tunnel pressure alters median nerve function in a dose-dependent manner: a rabbit model for carpal tunnel syndrome. J Orthop Res 2005; 23 (1) 218-223
• 6 Bland JDP. Carpal tunnel syndrome. Curr Opin Neurol 2005; 18 (5) 581-585
• 7 Gelberman RH, Seiler III JG, Rosenberg AE, Heyman P, Amiel D. Intercalary flexor tendon grafts. A morphological study of intrasynovial and extrasynovial donor tendons. Scand J Plast Reconstr Surg Hand Surg 1992; 26 (3) 257-264
• 8 Cohen MJ, Kaplan L. Histology and ultrastructure of the human flexor tendon sheath. J Hand Surg Am 1987; 12 (1) 25-29
• 9 Lundborg G, Rank F. Experimental intrinsic healing of flexor tendons based upon synovial fluid nutrition. J Hand Surg Am 1978; 3 (1) 21-31
• 10 Guimberteau JC. How is the anatomy adopted for tendon sliding? In New Ideas in Hand Flexor Tendon Surgery: The Sliding System, Vascularized Flexor Tendon Transfers. Pessac, France: Aquitaine Domaine Forestier; 2001: 47-90
• 11 Guimberteau JC, Delage JP, Wong J. The role and mechanical behavior of the connective tissue in tendon sliding. Chir Main 2010; 29 (3) 155-166
• 12 Ettema AM, Amadio PC, Zhao C, Wold LE, An KN. A histological and immunohistochemical study of the subsynovial connective tissue in idiopathic carpal tunnel syndrome. J Bone Joint Surg Am 2004; 86-A (7) 1458-1466
• 13 Zhao C, Ettema AM, Osamura N, Berglund LJ, An K-N, Amadio PC. Gliding characteristics between flexor tendons and surrounding tissues in the carpal tunnel: a biomechanical cadaver study. J Orthop Res 2007; 25 (2) 185-190
• 14 Kerr CD, Sybert DR, Albarracin NS. An analysis of the flexor synovium in idiopathic carpal tunnel syndrome: report of 625 cases. J Hand Surg Am 1992; 17 (6) 1028-1030
• 15 Ettema AM, Amadio PC, Zhao C , et al. Changes in the functional structure of the tenosynovium in idiopathic carpal tunnel syndrome: a scanning electron microscope study. Plast Reconstr Surg 2006; 118 (6) 1413-1422
• 16 Neal NC, McManners J, Stirling GA. Pathology of the flexor tendon sheath in the spontaneous carpal tunnel syndrome. J Hand Surg [Br] 1987; 12 (2) 229-232
• 17 Jinrok O, Zhao C, Amadio PC, An KN, Zobitz ME, Wold LE. Vascular pathologic changes in the flexor tenosynovium (subsynovial connective tissue) in idiopathic carpal tunnel syndrome. J Orthop Res 2004; 22 (6) 1310-1315
• 18 Oh J, Zhao C, Zobitz ME, Wold LE, An KN, Amadio PC. Morphological changes of collagen fibrils in the subsynovial connective tissue in carpal tunnel syndrome. J Bone Joint Surg Am 2006; 88 (4) 824-831
• 19 Lim JY, Cho SH, Han TR, Paik NJ. Dose-responsiveness of electrophysiologic change in a new model of acute carpal tunnel syndrome. Clin Orthop Relat Res 2004; (427) 120-126
• 20 Lluch AL. Thickening of the synovium of the digital flexor tendons: cause or consequence of the carpal tunnel syndrome?. J Hand Surg [Br] 1992; 17 (2) 209-212
• 21 Ettema AM, Zhao C, An K-N, Amadio PC. Comparative anatomy of the subsynovial connective tissue in the carpal tunnel of the rat, rabbit, dog, baboon, and human. Hand (NY) 2006; 1 (2) 78-84
• 22 Tung W-L, Zhao C, Yoshii Y, Su F-C, An K-N, Amadio PC. Comparative study of carpal tunnel compliance in the human, dog, rabbit, and rat. J Orthop Res 2010; 28 (5) 652-656
• 23 Yamaguchi T, Osamura N, Zhao C, Zobitz ME, An K-N, Amadio PC. The mechanical properties of the rabbit carpal tunnel subsynovial connective tissue. J Biomech 2008; 41 (16) 3519-3522
• 24 Oh S, Ettema AM, Zhao C , et al. Dextrose-induced subsynovial connective tissue fibrosis in the rabbit carpal tunnel: A potential model to study carpal tunnel syndrome?. Hand (NY) 2008; 3 (1) 34-40
• 25 Yoshii Y, Zhao C, Zhao KD, Zobitz ME, An K-N, Amadio PC. The effect of wrist position on the relative motion of tendon, nerve, and subsynovial connective tissue within the carpal tunnel in a human cadaver model. J Orthop Res 2008; 26 (8) 1153-1158
• 26 Yoshii Y, Zhao C, Schmelzer JD, Low PA, An K-N, Amadio PC. The effects of hypertonic dextrose injection on connective tissue and nerve conduction through the rabbit carpal tunnel. Arch Phys Med Rehabil 2009; 90 (2) 333-339
• 27 Yoshii Y, Zhao C, Schmelzer JD, Low PA, An K-N, Amadio PC. Effects of hypertonic dextrose injections in the rabbit carpal tunnel. J Orthop Res 2011; 29 (7) 1022-1027
• 28 Yoshii Y, Zhao C, Schmelzer JD, Low PA, An K-N, Amadio PC. Effects of multiple injections of hypertonic dextrose in the rabbit carpal tunnel: a potential model of carpal tunnel syndrome development. Hand (NY) 2014; 9 (1) 52-57
• 29 Yoshii Y, Zhao C, Henderson J, Zhao KD, An KN, Amadio PC. Shear strain and motion of the subsynovial connective tissue and median nerve during single-digit motion. J Hand Surg Am 2009; 34 (1) 65-73
• 30 Osamura N, Zhao C, Zobitz ME, An K-N, Amadio PC. Evaluation of the material properties of the subsynovial connective tissue in carpal tunnel syndrome. Clin Biomech (Bristol, Avon) 2007; 22 (9) 999-1003
• 31 Morizaki Y, Vanhees M, Thoreson AR , et al. The response of the rabbit subsynovial connective tissue to a stress-relaxation test. J Orthop Res 2012; 30 (3) 443-447
• 32 Moriya T, Zhao C, Cha SS , et al. Tendon injury produces changes in SSCT and nerve physiology similar to carpal tunnel syndrome in an in vivo rabbit model. Hand (NY) 2011; 6 (4) 399-407
• 33 Atroshi I, Gummesson C, Johnsson R, Ornstein E, Ranstam J, Rosén I. Prevalence of carpal tunnel syndrome in a general population. JAMA 1999; 282 (2) 153-158
• 34 Gelfman R, Melton III LJ, Yawn BP, Wollan PC, Amadio PC, Stevens JC. Long-term trends in carpal tunnel syndrome. Neurology 2009; 72 (1) 33-41
• 35 Marshall S, Tardif G, Ashworth N. Local corticosteroid injection for carpal tunnel syndrome. Cochrane Database Syst Rev 2007; (2) CD001554