Exposure‐dependent increases in IL‐1β, substance P, CTGF, and tendinosis in flexor digitorum tendons with upper extremity repetitive strain injury

Abstract

Upper extremity tendinopathies are associated with performance of forceful repetitive tasks. We used our rat model of repetitive strain injury to study changes induced in forelimb flexor digitorum tendons. Rats were trained to perform a high repetition high force (HRHF) handle-pulling task (12 reaches/min at 60 AE 5% maximum pulling force [MPF]), or a low repetition negligible force (LRNF) reaching and food retrieval task (three reaches/min at 5 AE 5% MPF), for 2 h/day in 30 min sessions, 3 days/week for 3-12 weeks. Forelimb grip strength was tested. Flexor digitorum tendons were examined at midtendon at the level of the carpal tunnel for interleukin (IL)-1b, neutrophil, and macrophage influx, Substance P, connective tissue growth factor (CTGF), and periostin-like factor (PLF) immunoexpression, and histopathological changes. In HRHF rats, grip strength progressively decreased, while IL-1b levels progressively increased in the flexor digitorum peritendon (para-and epitendon combined) and endotendon with task performance. Macrophage invasion was evident in week 6 and 12 HRHF peritendon but not endotendon. Also in HRHF rats, Substance P immunoexpression increased in week 12 peritendon as did CTGF-and PLF-immunopositive fibroblasts, the increased fibroblasts contributing greatly to peritendon thickening. Endotendon collagen disorganization was evident in week 12 HRHF tendons. LRNF tendons did not differ from controls, even at 12 weeks. Thus, we observed exposure-dependent changes in flexor digitorum tendons within the carpal tunnel, including increased inflammation, nociceptor-related neuropeptide immunoexpression, and fibrotic histopathology, changes associated with grip strength decline. Keywords: cytokines; inflammation; flexor digitorum tendon; repetitive task; PLF; CTGF; WMSD Tendinopathies of the hand and wrist tendons are associated with forceful repetition in the workplace. 1-3The incidence of flexor tenosynovitis is significantly higher in strenuous meat processing jobs: 25.3% for female packers, 16.8% for female sausage makers, and 12.5% for male meat cutters. The incidence in nonstrenuous jobs was less than 1% during a 31 month study period.4,5 Manufacturing workers performing highly repetitive and forceful jobs are 29 times more likely to develop wrist and hand tendonitis than workers performing low repetition and low force jobs. 5,6The etiology and pathophysiology of overuse-induced tendinopathies are still under investigation. Although the presence of an inflammatory component has not been identified by all investigators, 7-9 increased inflammatory molecules, for example, PGE 2 , have been found in tenosynovium of patients diagnosed with carpal tunnel syndrome (CTS), especially during the intermediate phase.10,11 However, PGE 2 was not found in tendon biopsies collected during the chronic painful tendinosis stage, although increased glutamate neurotransmitter and its receptor were evident. 8,9 The neurochemical Substance P is associated with chronic pain mediation 12 and has also been identif...

Increased CCN2, substance P and tissue fibrosis are associated with sensorimotor declines in a rat model of repetitive overuse injury

“…Past findings demonstrate increased nerve fibers in tissues as a consequence of repetitive tasks (Fedorczyk et al 2010;Kadi et al 1998;Lian et al 2006). SubP is a nociceptor-related neuropeptide (Henry 1982;Jessell 1982) that increases in several painful conditions, including painful tendinopathies, rotator cuff tears, and arthritis (Dean et al 2013;Gotoh et al 1998;Lui et al 2010;Munoz and Covenas 2011;Witonski et al 2005).…”

“…Adjacent sections of the NC, FRC and 18-week HRHF rat muscles were stained with hematoxylin and eosin (H&E), and with CD11b (a macrophage marker), using previously described methods (Fedorczyk et al 2010;Gao et al 2013). These sections were examined for the presence of neutrophils, lymphocytes or macrophages.…”

Ibuprofen as a Treatment for Work-Related Musculoskeletal Disorders: Effectiveness versus Caveats

“…Since we have observed that task-induced tissue inlammation precedes tissue ibrotic responses, including increased CTGF and collagen type 1 production [58][59][60], we next examined the efects of secondary ibuprofen treatment on ibrogenic processes in our rat model [40,61]. In addition to successful reductions of tissue and serum inlammatory responses after ibuprofen treatment, we observed signiicant reductions in TGFB-1 and CTGF protein expression as well as collagen deposition in median nerves ( Figure 3A) and lexor digitorum muscles of 6-week and 12-week HRHF+IBU rats (Figure 6) [40,61].…”

“…(K,L) Another stain (a Masson's trichrome stain, which shows collagen as blue) also shows that collagen deposition is increased between myoibers of 6-week HRHF rats compared to NC rats. Used by permission from Abdelmagid et al [60].…”

Systematic review of biochemical biomarkers for neck and upper-extremity musculoskeletal disorders

“…Comparatively fewer authors have researched MSD biomarkers in younger subjects with incipient disorders (40,41). Animal models would suggest that different biomarkers are present at different MSD stages and may differ by age (87)(88)(89). Various theories of MSD pathophysiology also suggest that differing biochemical biomarkers would occur at different MSD stages (21,82,90).…”