title: Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.
abstract: BACKGROUND
  Acute muscle injuries are exceedingly common and non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed to reduce the associated inflammation, swelling and pain that peak 1-2 days post-injury. While prophylactic use or early administration of NSAIDs has been shown to delay muscle regeneration and contribute to loss of muscle strength after healing, little is known about the effects of delayed NSAID use. Further, NSAID use following non-penetrating injury has been associated with increased risk and severity of infection, including that due to group A streptococcus, though the mechanisms remain to be elucidated. The present study investigated the effects of delayed NSAID administration on muscle repair and sought mechanisms supporting an injury/NSAID/infection axis.
  
  
  METHODS
  A murine model of eccentric contraction (EC)-induced injury of the tibialis anterior muscle was used to profile the cellular and molecular changes induced by ketorolac tromethamine administered 47 hr post injury.
  
  
  RESULTS
  NSAID administration inhibited several important muscle regeneration processes and down-regulated multiple cytoprotective proteins known to inhibit the intrinsic pathway of programmed cell death. These activities were associated with increased caspase activity in injured muscles but were independent of any NSAID effect on macrophage influx or phenotype switching.
  
  
  CONCLUSIONS
  These findings provide new molecular evidence supporting the notion that NSAIDs have a direct negative influence on muscle repair after acute strain injury in mice and thus add to renewed concern about the safety and benefits of NSAIDS in both children and adults, in those with progressive loss of muscle mass such as the elderly or patients with cancer or AIDS, and those at risk of secondary infection after trauma or surgery.
authors.affiliation: U.S. Department of Veterans Affairs, Office of Research and Development, Boise, ID, United States of America.|University of Washington School of Medicine, Seattle, WA, United States of America.
authors.forename: Amy E
authors.identifier: http://orcid.org/0000-0002-4143-1718
authors.initials: AE
authors.lastname: Bryant
authors.affiliation: U.S. Department of Veterans Affairs, Office of Research and Development, Boise, ID, United States of America.|Northwest Nazarene University, Nampa, ID, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Aldape
authors.affiliation: U.S. Department of Veterans Affairs, Office of Research and Development, Boise, ID, United States of America.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Bayer
authors.affiliation: U.S. Department of Veterans Affairs, Office of Research and Development, Boise, ID, United States of America.
authors.forename: Eva J
authors.initials: EJ
authors.lastname: Katahira
authors.affiliation: Boise State University, Boise, ID, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Bond
authors.affiliation: Pacific Northwest National Laboratory, Richland, WA, United States of America.
authors.forename: Carrie D
authors.initials: CD
authors.lastname: Nicora
authors.affiliation: Pacific Northwest National Laboratory, Richland, WA, United States of America.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Fillmore
authors.affiliation: Pacific Northwest National Laboratory, Richland, WA, United States of America.
authors.forename: Therese R W
authors.initials: TR
authors.lastname: Clauss
authors.affiliation: Pacific Northwest National Laboratory, Richland, WA, United States of America.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Metz
authors.affiliation: Pacific Northwest National Laboratory, Richland, WA, United States of America.
authors.forename: Bobbie-Jo
authors.initials: BJ
authors.lastname: Webb-Robertson
authors.affiliation: U.S. Department of Veterans Affairs, Office of Research and Development, Boise, ID, United States of America.|University of Washington School of Medicine, Seattle, WA, United States of America.
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Stevens
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000293:injuries*; D010641:Phenotype; D040901:Proteomics / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020169:Caspases