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The purpose of this systematic review was to compare corticosteroid injections with non-steroidal anti-inflammatory drug (NSAID) injections for musculoskeletal pain. The purpose was to determine if the treatment of musculoskeletal pain with corticosteroids is superior to NSAIDs in certain cases of severe pain. In addition, patients with severe pain may benefit from long-term use of corticosteroids as well. We report the results of the systematic review of randomized controlled trials conducted to compare corticosteroid injections with no treatment or treatment with no NSAIDs for musculoskeletal pain and to assess whether there is a better response among patients with severe pain. Methods We searched Medline, Embase, CINAHL, and Web of Science for eligible studies published from January 1966 to December 2015. We also searched the Cochrane Clinical Trials Registry (CENTRAL) using the terms 'corticosteroids', 'NSAID', 'pain', 'musculoskeletal pain', or 'arthritics' from January 1966 to December 2015. Of 876 references, we excluded 20 articles in the Cochrane Clinical Trials Registry. We reviewed references from the remaining articles and assessed for eligibility and risk of bias according to predetermined and validated guidelines (1). The quality of the evidence from each study was assessed by the WHO Committee on Systematic Reviews (2). Study Selection Studies which included patients with severe pain, including those patients with a history of knee osteoarthritis or radiculopathy, were included (n = 1 639). We included studies in which the treatment was compared with or without no treatment (n = 11 734). We included studies on the effect of NSAID only or no treatment (n = 10 584) and studies of two different non-Steroids NSAIDs (n = 40 895) in musculoskeletal pain (n = 20 977) (available from http://www.unboundmedicine.com). We included studies that compared corticosteroids with no treatment (n = 12 706). We excluded studies of the effect of a different NSAID for musculoskeletal pain (n = 8 637) or non-steroidal NSAIDs (n = 609). We also excluded studies where the treatment for the control group consisted only of a non-steroidal NSAID (n = 3 049). Only studies with blinded data collection during the first 12 months after the initiation of treatment were included (n = 534). We included studies by comparing patients with severe pain to non-musculoskeletal controls (n = 532 Related Article: