PNNL

Abstract

Acute muscle injuries are exceedingly common and non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed to reduce the associated pain and swelling. However, NSAIDs use can delay muscle regeneration, contribute to sustained loss of muscle strength and predispose injured muscles to secondary bacterial infection. To gain a more thorough understanding of the mechanisms responsible, a murine model of eccentric contraction (EC)-induced muscle injury was used to profile the cellular and molecular changes induced by ketorolac tromethamine (a non-selective NSAID) administered 48 hr post injury. Results provide new evidence that ketorolac promotes a pro-apoptosis phenotype in injured muscles by down-regulating several key anti-apoptosis proteins that regulate the intrinsic pathway of programmed cell death and suggest new signaling targets for further study of NSAID action. These deleterious effects of NSAIDs on muscle physiology add to renewed concern about the safety of these agents. Acute muscle strains are exceedingly common and are associated with delayed-onset muscle soreness (DOMS) that occurs 1-2 days post-injury (reviewed in (12)). Though non-steroidal anti-inflammatory drugs (NSAIDs) decrease the associated pain and swelling, recent evidence suggests NSAIDs delay muscle regeneration (53; 54), reduce muscle strength after healing (32) and predispose to bacterial infection (20). The mechanisms are largely undefined and few studies have examined the effects of NSAID consumption during DOMS on regeneration after injury. Thus, we used an experimental model of eccentric contraction (EC)-induced strain of the tibialis anterior (TA) muscle to investigate the cellular and proteomic profiles of regenerating muscle in the presence and absence of ketorolac tromethamine, a non-selective NSAID, given 48 hr after injury.