title: Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task.
abstract: Systemic inflammation is known to induce sickness behaviors, including decreased social interaction and pain. We have reported increased serum inflammatory cytokines in a rat model of repetitive strain injury (rats perform an upper extremity reaching task for prolonged periods). Here, we sought to determine if sickness behaviors are induced in this model and the effectiveness of conservative treatments.
  
  
  
  Experimental rats underwent initial training to learn a high force reaching task (10 min/day, 5 days/week for 6 weeks), with or without ibuprofen treatment (TRHF vs. TRHF + IBU rats). Subsets of trained animals went on to perform a high repetition high force (HRHF) task for 6 or 12 weeks (2 h/day, 3 days/week) without treatment, or received two secondary interventions: ibuprofen (HRHF + IBU) or a move to a lower demand low repetition low force task (HRHF-to-LRLF), beginning in task week 5. Mixed-effects models with repeated measures assays were used to assay duration of social interaction, aggression, forepaw withdrawal thresholds and reach performance abilities. One-way and two-way ANOVAs were used to assay tissue responses. Corrections for multiple comparisons were made.
  
  
  
  TRHF + IBU rats did not develop behavioral declines or systemic increases in IL-1beta and IL-6, observed in untreated TRHF rats. Untreated HRHF rats showed social interaction declines, difficulties performing the operant task and forepaw mechanical allodynia. Untreated HRHF rats also had increased serum levels of several inflammatory cytokines and chemokines, neuroinflammatory responses (e.g., increased TNFalpha) in the brain, median nerve and spinal cord, and Substance P and neurokinin 1 immunoexpression in the spinal cord. HRHF + IBU and HRHF-to-LRLF rats showed improved social interaction and reduced inflammatory serum, nerve and brain changes. However, neither secondary treatment rescued HRHF-task induced forepaw allodynia, or completely attenuated task performance declines or spinal cord responses.
  
  
  
  These results suggest that inflammatory mechanisms induced by prolonged performance of high physical demand tasks mediate the development of social interaction declines and aggression. However, persistent spinal cord sensitization was associated with persistent behavioral indices of discomfort, despite use of conservative secondary interventions indicating the need for prevention or more effective interventions.
authors.affiliation: Department of Surgery, University of Pennsylvania, 3450 Hamilton Walk, Philadelphia, PA, 19104, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Xin
authors.affiliation: Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, Umeå University, Umeå, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Hadrévi
authors.affiliation: Department of Neurosurgery, Thomas Jefferson University, 1020 Locust St., Philadelphia, PA, 19107, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Elliott
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, 3500 North Broad St., Philadelphia, PA, 19140, USA.
authors.forename: M
authors.initials: M
authors.lastname: Amin
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, 3500 North Broad St., Philadelphia, PA, 19140, USA.
authors.forename: M Y
authors.initials: MY
authors.lastname: Harris
authors.affiliation: College of Health Professions, Pacific University, 190 SE 8th Avenue, Hillsboro, OR, 97123, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Barr-Gillespie
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, 3500 North Broad St., Philadelphia, PA, 19140, USA. mary.barbe@temple.edu.
authors.forename: M F
authors.initials: MF
authors.lastname: Barbe
mesh_terms: D000374:Aggression; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000276:immunology / Q000473:pathology; D000072700:Conservative Treatment / Q000379:methods; D012090:Cumulative Trauma Disorders / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D005552:Forelimb / Q000293:injuries* / Q000503:physiopathology; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D007052:Ibuprofen / Q000494:pharmacology; D055809:Illness Behavior; D008475:Median Nerve / Q000276:immunology / Q000473:pathology; D010146:Pain / Q000503:physiopathology; D059408:Pain Management; D017288:Pain Threshold; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012919:Social Behavior; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013997:Time Factors
chemical_list: D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D007052:Ibuprofen
keywords: Aggression; Cytokines; Inflammation; Mechanical hypersensitivity; Repetitive loading; Social interaction; Upper extremity; Von Frey; Work-related musculoskeletal disorders