Clinicians and patients can choose various pain relief options to help ease and manage acute pain from non–low back musculoskeletal injuries. This systematic review was conducted to assess outpatient treatments’ comparative effectiveness for acute pain from non–low back musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs). The data sources were taken from EMBASE, CINAHL, MEDLINE, Cochrane Central Register of Controlled Trials, and PEDro (Physiotherapy Evidence Database) up to January 2nd, 2020.

Pairs of reviewers independently extracted data and identified interventional RCTs that enrolled patients presenting pain of up to 4 weeks’ duration from non–low back musculoskeletal injuries.

The certainty of the evidence was then evaluated by using the GRADE approach system.

The eligible studies, 207 in number, included about 33,000 participants and with the evaluation of 45 therapies. Amongst all studies, 99 involved populations with musculoskeletal injuries, 59 with sprains, 13 with whiplash, and 11 with muscle strains. The remaining included various injuries ranging from fractures to minor bruises. Topical nonsteroidal anti-inflammatory agents proved to have the greatest benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Opioids, as compared with placebo, acetaminophen, plus an opioid, helped manage intermediate pain. Ultimately, tramadol was ineffective, and opioids increased the risk of gastrointestinal and neurological damage.

In conclusion, this review found high to moderately certain evidence that tramadol failed to achieve essential benefits, and opioids caused more adverse events than placebo. The results demonstrate that opioids fail to achieve benefits beyond interventions with less harm and provide more reasons to avoid prescribing opioids for pain management from acute non–low back musculoskeletal injury.