title: MMP-2 expression is associated with rapidly proliferative arteriosclerosis in the flexor tenosynovium and pain severity in carpal tunnel syndrome.
abstract: Due to the lack of correlation between symptom severity and electrophysiology or nerve function, the 'container hypothesis' has emerged as a new concept in carpal tunnel syndrome (CTS). This proposes that symptoms relate to connective tissue alteration rather than to nerve fibre pathology. This study was conducted to investigate the pathology of the flexor tenosynovium and its relationship with symptomatology. The subjects comprised 40 patients with electrophysiologically proven CTS who underwent open carpal tunnel release (age range: 31-79 years). In all patients, subjective symptom severity was assessed with a Likert scale and symptom duration was recorded preoperatively. Flexor tenosynovium biopsied during surgery was analysed for arterial and connective tissue alteration. Proliferative arteriosclerosis was graded using the modified Banff score. Gelatin zymography and immunohistochemistry were also performed to investigate the role of gelatinase in CTS. Relationships were evaluated using Spearman rank correlation coefficients. Proliferative arteriosclerosis occurred with disease progression in the flexor tenosynovium, in the absence of inflammation. This event did not correlate with patient age but correlated closely with symptom duration. Immunohistochemistry with antibodies against MMP-2 and elastic van Gieson staining revealed that arterioles express high levels of MMP-2 within 3 months of symptom onset and that intimal hyperplasia proceeded rapidly between 4 and 7 months, resulting in severe vascular narrowing. Gelatin zymography showed that MMP-2 activity correlated negatively with symptom duration and positively with pain severity.
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, Mie University-Tsu, Mie, Japan. h-hirata@clin.medic.mie-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hirata
authors.forename: Masaya
authors.initials: M
authors.lastname: Tsujii
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Kyoko
authors.initials: K
authors.lastname: Imanaka-Yoshida
authors.forename: Akimasa
authors.initials: A
authors.lastname: Morita
authors.forename: Noritaka
authors.initials: N
authors.lastname: Okuyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagakura
authors.forename: Toshiko
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Kohzo
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Uchida
mesh_terms: D000328:Adult; D000368:Aged; D001160:Arterioles / Q000473:pathology; D001161:Arteriosclerosis / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D002349:Carpal Tunnel Syndrome / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D008875:Middle Aged; D010146:Pain / Q000473:pathology / Q000503:physiopathology*; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000473:pathology / Q000503:physiopathology; D013710:Tendons / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology
chemical_list: D020778:Matrix Metalloproteinase 2