title: The interaction of force and repetition on musculoskeletal and neural tissue responses and sensorimotor behavior in a rat model of work-related musculoskeletal disorders.
abstract: BACKGROUND
  We examined the relationship of musculoskeletal risk factors underlying force and repetition on tissue responses in an operant rat model of repetitive reaching and pulling, and if force x repetition interactions were present, indicative of a fatigue failure process. We examined exposure-dependent changes in biochemical, morphological and sensorimotor responses occurring with repeated performance of a handle-pulling task for 12 weeks at one of four repetition and force levels: 1) low repetition with low force, 2) high repetition with low force, 3) low repetition with high force, and 4) high repetition with high force (HRHF).
  
  
  METHODS
  Rats underwent initial training for 4-6 weeks, and then performed one of the tasks for 12 weeks, 2 hours/day, 3 days/week. Reflexive grip strength and sensitivity to touch were assayed as functional outcomes. Flexor digitorum muscles and tendons, forelimb bones, and serum were assayed using ELISA for indicators of inflammation, tissue stress and repair, and bone turnover. Histomorphometry was used to assay macrophage infiltration of tissues, spinal cord substance P changes, and tissue adaptative or degradative changes. MicroCT was used to assay bones for changes in bone quality.
  
  
  RESULTS
  Several force x repetition interactions were observed for: muscle IL-1alpha and bone IL-1beta; serum TNFalpha, IL-1alpha, and IL-1beta; muscle HSP72, a tissue stress and repair protein; histomorphological evidence of tendon and cartilage degradation; serum biomarkers of bone degradation (CTXI) and bone formation (osteocalcin); and morphological evidence of bone adaptation versus resorption. In most cases, performance of the HRHF task induced the greatest tissue degenerative changes, while performance of moderate level tasks induced bone adaptation and a suggestion of muscle adaptation. Both high force tasks induced median nerve macrophage infiltration, spinal cord sensitization (increased substance P), grip strength declines and forepaw mechanical allodynia by task week 12.
  
  
  CONCLUSIONS
  Although not consistent in all tissues, we found several significant interactions between the critical musculoskeletal risk factors of force and repetition, consistent with a fatigue failure process in musculoskeletal tissues. Prolonged performance of HRHF tasks exhibited significantly increased risk for musculoskeletal disorders, while performance of moderate level tasks exhibited adaptation to task demands.
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, 3500 North Broad St, Philadelphia 19140, PA, USA. mary.barbe@temple.edu.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Barbe
authors.forename: Sean
authors.initials: S
authors.lastname: Gallagher
authors.forename: Vicky S
authors.initials: VS
authors.lastname: Massicotte
authors.forename: Michael
authors.initials: M
authors.lastname: Tytell
authors.forename: Steven N
authors.initials: SN
authors.lastname: Popoff
authors.forename: Ann E
authors.initials: AE
authors.lastname: Barr-Gillespie
mesh_terms: D000818:Animals; D016723:Bone Remodeling; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002356:Cartilage / Q000473:pathology; D024042:Collagen Type I / Q000097:blood; D003216:Conditioning, Operant; D012090:Cumulative Trauma Disorders / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D053580:Muscle Strength; D009140:Musculoskeletal Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D009141:Musculoskeletal System / Q000378:metabolism*; D009417:Nerve Tissue / Q000378:metabolism*; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000097:blood; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D055114:X-Ray Microtomography
chemical_list: D024042:Collagen Type I; D016207:Cytokines; D050884:HSP72 Heat-Shock Proteins; D010455:Peptides; D010982:Platelet-Derived Growth Factor; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat