Debate exists regarding the relative role of various biomechanical factors (e.g., force, repetition, acceleration, etc.) during repetitive work in the causation of upper extremity musculoskeletal disorders. Most of these factors can be altered in the design of work. We will use our recently developed rabbit finger flexor model to investigate the role of these factors in causing entrapment neuropathy of the median nerve at the wrist and tendinosis at the epicondyle. In addition, the study will identify early cellular and biochemical changes in matrix proteins and cytokines. For 2 hours per day, 3 days per week for 10 weeks, the large finger flexor is repetitively stimulated while the fingertip load is controlled. The loading is performed under general anesthesia. The system allows for the precise control of repetition rate, peak fingertip force, load duration, and rate of loading. Three experiments will separately investigate the role of repetition rate, peak force, and loading rate on tissue function and structure. Work (integral of force over time) will be held constant across the loading conditions. Median nerve function is evaluated by measuring distal motor latency across the wrist, and morphologic differences in nerve fiber count, fiber density and myeination are quantified. Morphologic differences in the tendon attachment site at the epicondyle are evaluated with semi-quantitative and quantitative methods assessing cellularity, cell shape, collagen fiber linearity, neovascularization, edema, and apoptosis. The antigentic location and density of structural proteins (collagen I,II, ifi, decorin, tenascin, fibronectin), and various cytokines (IL- lb. TNF-a, TGF-B, bFGF, substance P) will be assessed using immunohistochemical methods. A fourth experiment will assess these biochemical endpoints at earlier times of exposure. This study has the potential to identify the characteristics of biomechanical loading, which are injurious; information valuable to occupational health practitioners in adding specificity to ergonomic guidelines for repetitive work. The study also has the potential to identify the biochemical pathways and time-frames of disease progression; information which may lead to new strategies for treating and preventing entrapment neuropathies and tendon disorders related to work.

Agency
National Institute of Health (NIH)
Institute
National Institute for Occupational Safety and Health (NIOSH)
Type
Research Project (R01)
Project #
5R01OH007359-04
Application #
6771135
Study Section
Safety and Occupational Health Study Section (SOH)
Program Officer
Frederick, Linda J
Project Start
2001-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2006-06-30
Support Year
4
Fiscal Year
2004
Total Cost
$217,481
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Harris, Carisa; Eisen, Ellen A; Goldberg, Robert et al. (2011) 1st place, PREMUS best paper competition: workplace and individual factors in wrist tendinosis among blue-collar workers--the San Francisco study. Scand J Work Environ Health 37:85-98
Asundi, Krishna R; Rempel, David M (2008) MMP-1, IL-1beta, and COX-2 mRNA expression is modulated by static load in rabbit flexor tendons. Ann Biomed Eng 36:237-43
Asundi, Krishna R; King, Karen B; Rempel, David M (2008) Evaluation of gene expression through qRT-PCR in cyclically loaded tendons: an in vivo model. Eur J Appl Physiol 102:265-70
Asundi, Krishna R; Rempel, David M (2008) Cyclic loading inhibits expression of MMP-3 but not MMP-1 in an in vitro rabbit flexor tendon model. Clin Biomech (Bristol, Avon) 23:117-21
Asundi, Krishna R; Kursa, Kathy; Lotz, Jeff et al. (2007) In vitro system for applying cyclic loads to connective tissues under displacement or force control. Ann Biomed Eng 35:1188-95
Nakama, Leena H; King, Karen B; Abrahamsson, Sven et al. (2007) Effect of repetition rate on the formation of microtears in tendon in an in vivo cyclical loading model. J Orthop Res 25:1176-84
Nakama, Leena H; King, Karen B; Abrahamsson, Sven et al. (2006) VEGF, VEGFR-1, and CTGF cell densities in tendon are increased with cyclical loading: An in vivo tendinopathy model. J Orthop Res 24:393-400
Keir, Peter J; Rempel, David M (2005) Pathomechanics of peripheral nerve loading. Evidence in carpal tunnel syndrome. J Hand Ther 18:259-69
Nakama, Leena H; King, Karen B; Abrahamsson, Sven et al. (2005) Evidence of tendon microtears due to cyclical loading in an in vivo tendinopathy model. J Orthop Res 23:1199-205
King, K B; Opel, C F; Rempel, D M (2005) Cyclical articular joint loading leads to cartilage thinning and osteopontin production in a novel in vivo rabbit model of repetitive finger flexion. Osteoarthritis Cartilage 13:971-8

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