There is debate as to whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is beneficial after acute skeletal muscle injury. Some studies have suggested that NSAID use may be detrimental to injured muscle.
Purpose:
To determine whether NSAID use affects recovery from skeletal muscle injury as assessed by strength loss, soreness, and/or blood creatine kinase level.
Study Design:
Systematic review and meta-analysis.
Methods:
An extensive systematic review was completed searching 16 databases (eg, PubMed, Cochrane Library, EMBASE). Inclusion criteria were (1) acute injury to skeletal muscle, (2) use of a control condition, (3) certainty of the NSAID dose administered, and (4) use of 1 or more of the 3 desired outcome measures. A total of 5343 study reports were screened, of which 41 studies were deemed suitable for inclusion. The standardized mean difference was used as the effect size (ES) and was calculated such that a positive ES indicated NSAID efficacy. Meta-analyses were run using a random-effects model.
Results:
For all studies, time points after injury, and injury markers combined, NSAID use was found to elicit a small to medium, significant decrease in the markers of injury (overall ES = +0.34; P = .0001). Because heterogeneity in study ES was apparent (ie, Q−df = 52.4, P = .000005; I2 = 57%), subgroup meta-analyses and meta-regressions were run in an attempt to explain the heterogeneity. In human studies, study ESs were higher when lower body muscles were injured (P = .045). In animal studies, study ESs were lower with longer NSAID administration durations (P = .023) and at longer follow-up times after injury (P = .010).
Conclusion:
Overall, our analysis supports NSAID use for reducing strength loss, soreness, and blood creatine kinase level after an acute muscle injury, at least for humans and in the short term. Additional research is required to determine why NSAID use appears to be more effective when lower-body muscles in humans are injured. It would also be important to determine why NSAID use appears detrimental at later times after injury in animals but not humans.
ArmstrongRBWarrenGLWarrenJA. Mechanisms of exercise-induced muscle fibre injury. Sports Med. 1991;12(3):184-207.
2.
BaldwinACStevensonSWDudleyGA. Nonsteroidal anti-inflammatory therapy after eccentric exercise in healthy older individuals. J Gerontol A Biol Sci Med Sci. 2001;56(8):M510-513.
3.
BaldwinLanier A. Use of nonsteroidal anti-inflammatory drugs following exercise-induced muscle injury. Sports Med. 2003;33(3):177-185.
4.
BarlasPCraigJARobinsonJWalshDMBaxterGDAllenJM. Managing delayed-onset muscle soreness: lack of effect of selected oral systemic analgesics. Arch Phys Med Rehabil. 2000;81(7):966-972.
5.
BondesenBAMillsSTKegleyKMPavlathGK. The COX-2 pathway is essential during early stages of skeletal muscle regeneration. Am J Physiol Cell Physiol. 2004;287(2):C475-483.
6.
BondesenBAMillsSTPavlathGK. The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms. Am J Physiol Cell Physiol. 2006;290(6):C1651-1659.
7.
BorensteinMHedgesLVHigginsJRothsteinHR. Introduction to Meta-analysis. West Sussex, UK: Wiley; 2009.
8.
BourgeoisJMacDougallDMacDonaldJTarnopolskyM. Naproxen does not alter indices of muscle damage in resistance-exercise trained men. Med Sci Sports Exerc. 1999;31(1):4-9.
9.
BricksonSJiLLSchellKOlabisiRSt Pierre SchneiderBBestTM. M1/70 attenuates blood-borne neutrophil oxidants, activation, and myofiber damage following stretch injury. J Appl Physiol. 2003;95(3):969-976.
10.
ChouRMcDonaghMSNakamotoEGriffinJ. Analgesics for osteoarthritis: an update of the 2006 comparative effectiveness review. Comparative Effectiveness Review No. 38 (prepared by the Oregon Evidence-based Practice Center under Contract No. HHSA 290 2007 10057 I). AHRQ Publication No. 11(12)-EHC076-EF. Rockville, MD: Agency for Healthcare Research and Quality (US); 2011:A-1. www.effectivehealthcare.ahrq.gov/reports/final.cfm. Accessed May 27, 2015.
11.
CohenJ. Statistical Power Analysis for the Behavioral Sciences. Hillsdale, NJ: Lawrence Erlbaum Associates; 1988:567.
12.
CroisierJLCamusGMonfilsTet al. Piroxicam fails to reduce myocellular enzyme leakage and delayed onset muscle soreness induced by isokinetic eccentric exercise. Mediators Inflamm. 1996;5(3):230-234.
13.
CryerB. NSAID-associated deaths: the rise and fall of NSAID-associated GI mortality. Am J Gastroenterol. 2005;100(8):1694-1695.
14.
De CarliAVolpiPPelosiniIet al. New therapeutic approaches for management of sport-induced muscle strains. Adv Ther. 2009;26(12):1072-1083.
15.
DermanW. Does pre-treatment with non-steroidal antiinflammatory drugs prevent muscle pain and damage after unaccustomed eccentric exercise? [abstract]Br J Sports Med2008;42:506.
16.
DonnellyAEMaughanRJWhitingPH. Effects of ibuprofen on exercise-induced muscle soreness and indices of muscle damage. Br J Sports Med. 1990;24(3):191-195.
17.
DonnellyAEMcCormickKMaughanRJWhitingPHClarksonPM. Effects of a non-steroidal anti-inflammatory drug on delayed onset muscle soreness and indices of damage. Br J Sports Med. 1988;22(1):35-38.
18.
DudleyGACzerkawskiJMeinrodAGillisGBaldwinAScarponeM. Efficacy of naproxen sodium for exercise-induced dysfunction muscle injury and soreness. Clin J Sport Med. 1997;7(1):3-10.
19.
FaulknerJABrooksSVOpiteckJA. Injury to skeletal muscle fibers during contractions: conditions of occurrence and prevention. Phys Ther. 1993;73(12):911-921.
20.
FrancisKTHooblerT. Effects of aspirin on delayed muscle soreness. J Sports Med Phys Fitness. 1987;27(3):333-337.
21.
GehrigSMLynchGS. Emerging drugs for treating skeletal muscle injury and promoting muscle repair. Expert Opin Emerg Drugs. 2011;16(1):163-182.
22.
GrossmanJMArnoldBLPerrinDHKahlerDM. Effect of ibuprofen use on delayed onset muscle soreness of the elbow flexors. J Sport Rehabil. 1995;4:253-263.
23.
GulickDT. Effects of Various Treatment Techniques on the Signs and Symptoms of Delayed Onset Muscle Soreness [dissertation]. Ann Arbor, MI: Temple University; 1996.
24.
HallRde AntuenoCWebberA, Canadian Research Ethics B. Publication bias in the medical literature: a review by a Canadian Research Ethics Board. Can J Anaesth. 2007;54(5):380-388.
25.
HassonSMDanielsJCDivineJGet al. Effect of ibuprofen use on muscle soreness, damage, and performance: a preliminary investigation. Med Sci Sports Exerc. 1993;25(1):9-17.
26.
HigginsJPAltmanDGGotzschePCet al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
27.
HopewellSClarkeMMalletS. Grey literature and systematic reviews. In: RothsteinHRSuttonAJBorensteinM, eds. Publication Bias in Meta-analysis. West Sussex, UK: Wiley; 2005:49-72.
28.
HopewellSLoudonKClarkeMJOxmanADDickersinK. Publication bias in clinical trials due to statistical significance or direction of trial results. Cochrane Database Syst Rev. 2009(1):MR000006.
29.
HowellJNConatserRRChlebounGSKarapondoDLChilaAG. The effect of nonsteroidal anti-inflammatory drugs on recovery from exercise-induced muscle injury, part 2: ibuprofen. J Musculoskelet Pain. 1998;6(4):69-83.
30.
HowellJNConatserRRChlebounGSKarapondoDLChilaAG. The effect of nonsteroidal anti-inflammatory drugs on recovery from exercise-induced muscle injury, part 1: fluriprofen. J Musculoskelet Pain. 1998;6(4):59-68.
31.
KellettJ. Acute soft tissue injuries—a review of the literature. Med Sci Sports Exerc. 1986;18(5):489-500.
32.
KraemerWJGomezALRatamessNAet al. Effects of vicoprofen and ibuprofen on anaerobic performance after muscle damage. J Sport Rehabil. 2002;11(2):104-119.
33.
KuipersHKeizerHAVerstappenFTCostillDL. Influence of a prostaglandin-inhibiting drug on muscle soreness after eccentric work. Int J Sports Med. 1985;6(6):336-339.
34.
KyzasPALoizouKTIoannidisJP. Selective reporting biases in cancer prognostic factor studies. J Natl Cancer Inst. 2005;97(14):1043-1055.
35.
LapointeBMFremontPCoteCH. Adaptation to lengthening contractions is independent of voluntary muscle recruitment but relies on inflammation. Am J Physiol Regul Integr Comp Physiol. 2002;282(1):R323-329.
36.
LapointeBMFremontPCoteCH. Influence of nonsteroidal anti-inflammatory drug treatment duration and time of onset on recovery from exercise-induced muscle damage in rats. Arch Phys Med Rehabil. 2003;84(5):651-655.
37.
LapointeBMFrenetteJCoteCH. Lengthening contraction-induced inflammation is linked to secondary damage but devoid of neutrophil invasion. J Appl Physiol. 2002;92(5):1995-2004.
38.
LecomteJMLacroixVJMontgomeryDL. A randomized controlled trial of the effect of naproxen on delayed onset muscle soreness and muscle strength. Clin J Sport Med. 1998;8(2):82-87.
39.
MackRL. The Efficacy of Topical Ibuprofen in an Anti-inflammatory Model: Delayed Onset Muscle Soreness [master’s thesis]. Vancouver, BC: University of British Columbia1995:88p.
40.
MackeyALKjaerMDandanellSet al. The influence of anti-inflammatory medication on exercise-induced myogenic precursor cell responses in humans. J Appl Physiol. 2007;103(2):425-431.
41.
MeamarbashiARajabiA. Preventive effects of 10-day supplementation with saffron and indomethacin on the delayed-onset muscle soreness. Clin J Sport Med. 2015;25(2):105-112.
42.
MehalloCJDreznerJABytomskiJR. Practical management: nonsteroidal antiinflammatory drug (NSAID) use in athletic injuries. Clin J Sport Med. 2006;16(2):170-174.
43.
MikkelsenURLangbergHHelmarkICet al. Local NSAID infusion inhibits satellite cell proliferation in human skeletal muscle after eccentric exercise. J Appl Physiol. 2009;107(5):1600-1611.
44.
MishraDKFridenJSchmitzMCLieberRL. Anti-inflammatory medication after muscle injury: a treatment resulting in short-term improvement but subsequent loss of muscle function. J Bone Joint Surg Am. 1995;77(10):1510-1519.
45.
MoherDLiberatiATetzlaffJAltmanDGGroupP. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.
46.
O’GradyMHackneyACSchneiderKet al. Diclofenac sodium (Voltaren) reduced exercise-induced injury in human skeletal muscle. Med Sci Sports Exerc. 2000;32(7):1191-1196.
47.
ObremskyWTSeaberAVRibbeckBMGarrettWEJr. Biomechanical and histologic assessment of a controlled muscle strain injury treated with piroxicam. Am J Sports Med. 1994;22(4):558-561.
48.
OtisJSBurkholderTJPavlathGK. Stretch-induced myoblast proliferation is dependent on the COX2 pathway. Exp Cell Res. 2005;310(2):417-425.
49.
PaulsenGEgnerIMDrangeMet al. A COX-2 inhibitor reduces muscle soreness, but does not influence recovery and adaptation after eccentric exercise. Scand J Med Sci Sports. 2010;20(1):e195-207.
50.
PetersJLSuttonAJJonesDRAbramsKRRushtonL. Performance of the trim and fill method in the presence of publication bias and between-study heterogeneity. Stat Med. 2007;26(25):4544-4562.
51.
PizzaFXCavenderDStockardABayliesHBeighleA. Anti-inflammatory doses of ibuprofen: effect on neutrophils and exercise-induced muscle injury. Int J Sports Med. 1999;20(2):98-102.
52.
PizzaFXPetersonJMBaasJHKohTJ. Neutrophils contribute to muscle injury and impair its resolution after lengthening contractions in mice. J Physiol. 2005;562(pt 3):899-913.
53.
RahnamaNRahmani-NiaFEbrahimK. The isolated and combined effects of selected physical activity and ibuprofen on delayed-onset muscle soreness. J Sports Sci. 2005;23(8):843-850.
54.
RamosLLealECPallottaRCet al. Infrared (810 nm) low-level laser therapy in experimental model of strain-induced skeletal muscle injury in rats: effects on functional outcomes. Photochem Photobiol. 2012;88:154-160.
55.
ReynoldsJFNoakesTDSchwellnusMPWindtABowerbankP. Non-steroidal anti-inflammatory drugs fail to enhance healing of acute hamstring injuries treated with physiotherapy. S Afr Med J. 1995;85(6):517-522.
56.
RotherMSeidelEJClarksonPMMazgareanuSVierlURotherI. Efficacy of epicutaneous Diractin (ketoprofen in Transfersome gel) for the treatment of pain related to eccentric muscle contractions. Drug Des Devel Ther. 2009;3:143-149.
57.
SayersSPKnightCAClarksonPMVan WegenEHKamenG. Effect of ketoprofen on muscle function and sEMG activity after eccentric exercise. Med Sci Sports Exerc. 2001;33(5):702-710.
58.
SmithLLGeorgeRTChenierTCet al. Do over the counter analgesics reduce delayed onset muscle soreness and serum creatine kinase values?Sports Med Training Rehab. 1995;6(2):81-88.
59.
StoneMBMerrickMAIngersollCDEdwardsJE. Preliminary comparison of bromelain and ibuprofen for delayed onset muscle soreness management. Clin J Sport Med. 2002;12(6):373-378.
60.
StoneMBPalmieriRMIngersollCD. The role of non-steroidal anti-inflammatory drugs for the treatment of delayed onset muscle soreness in sport. Int J Sports Med. 2004;5(2):147-154.
61.
SuttonAJ. Publication Bias. New York, NY: Russell Sage Foundation; 2009:435-452.
62.
SvenssonPHoueLArendt-NielsenL. Effect of systemic versus topical nonsteroidal anti-inflammatory drugs on postexercise jaw-muscle soreness: a placebo-controlled study. J Orofac Pain. 1997;11(4):353-362.
63.
TerrinNSchmidCHLauJOlkinI. Adjusting for publication bias in the presence of heterogeneity. Stat Med. 2003;22(13):2113-2126.
64.
TokmakidisSPKokkinidisEASmiliosIDoudaH. The effects of ibuprofen on delayed muscle soreness and muscular performance after eccentric exercise. J Strength Cond Res. 2003;17(1):53-59.
65.
TrappeTAWhiteFLambertCPCesarDHellersteinMEvansWJ. Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Am J Physiol Endocrinol Metab. 2002;282(3):E551-556.
66.
Van HeestJLStoppaniJScheetTPet al. Effects of ibuprofen and vicoprofen (R) on physical performance after exercise-induced muscle damage. J Sport Rehabil. 2002;11:224-234.
67.
VejaranoME. Effect of a Non-steroidal, Anti-inflammatory Drug (Indocin) on Selected Parameters of Muscular Function Following Concentric and Eccentric Work [master’s thesis]. Blacksburg, VA: Virginia Polytechnic Institute and State University; 1985.
68.
VignaudACebrianJMartellyICaruelleJPFerryA. Effect of anti-inflammatory and antioxidant drugs on the long-term repair of severely injured mouse skeletal muscle. Exp Physiol. 2005;90(4):487-495.
69.
WarrenGLCallJAFarthingAKBaddom-PiaroB. Minimal evidence for a secondary loss of strength after an acute muscle injury: a systematic review and meta-analysis. Sports Med. 2017;47(1):41-59.
70.
WarrenGLHuldermanTJensenNet al. Physiological role of tumor necrosis factor alpha in traumatic muscle injury. FASEB J. 2002;16(12):1630-1632.
71.
WarrenGLHuldermanTMishraDet al. Chemokine receptor CCR2 involvement in skeletal muscle regeneration. FASEB J. 2005;19(3):413-415.
72.
WarrenGLLoweDAArmstrongRB. Measurement tools used in the study of eccentric contraction-induced injury. Sports Med. 1999;27(1):43-59.
73.
WarrenGLO’FarrellLSummanMet al. Role of CC chemokines in skeletal muscle functional restoration after injury. Am J Physiol Cell Physiol. 2004;286(5):C1031-1036.
74.
WarrenGLPalubinskasLE. Human and animal experimental muscle injury models. In: TiidusPM, ed. Skeletal Muscle Damage and Repair. Champaign, IL: Human Kinetics; 2008:13-36.
75.
WarrenGLParkNDMarescaRDMcKibansKIMillard-StaffordML. Effect of caffeine ingestion on muscular strength and endurance: a meta-analysis. Med Sci Sports Exerc. 2010;42(7):1375-1387.
76.
ZiltenerJLLealSFournierPE. Non-steroidal anti-inflammatory drugs for athletes: an update. Ann Phys Rehabil Med. 2010;53(4):278-282, 282-288.
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