Cochrane in CORR®: Oral Nonsteroidal Anti-inflammatory Drugs versus Other Oral Analgesic Agents for Acute Soft Tissue Injury : Clinical Orthopaedics and Related Research®

Secondary Logo

Journal Logo


Cochrane in CORR®: Oral Nonsteroidal Anti-inflammatory Drugs versus Other Oral Analgesic Agents for Acute Soft Tissue Injury

Madden, Kim PhD; Busse, Jason W. DC, PhD

Author Information
Clinical Orthopaedics and Related Research 479(1):p 17-23, January 2021. | DOI: 10.1097/CORR.0000000000001595
  • Free

Importance of the Topic

Acute soft tissue injuries like sprains, strains, and contusions are common injuries that often require medical attention. A population-based study in the United Kingdom showed that the incidence of ankle sprains presenting to emergency departments was 53 to 60 per 10,000 [1]. There were 12.5 million emergency department visits for strains, sprains, contusions, and superficial soft tissue injuries in the United States in 2010 [5], leading to USD 25 billion in medical costs and USD 31.5 billion in work loss costs [5]. Although minor soft tissue injuries resolve with nonsurgical care, some severe ones can require surgery, while others can result in long-term morbidity and persistent pain. For example, up to 30% of ankle sprains will develop chronic instability [11], and 13% of ankle osteoarthritis is attributable to ligament damage [12]. This highlights the importance of effective, early management.

Many patients with soft tissue injuries receive opioid pain medications. For example, a 2018 population-based study [8] found that 25% of opioid-naïve patients with ankle sprains receive an opioid prescription. However, this practice is under increased scrutiny lately because of the risk of addiction. A recent review of 14 studies with 13,263,393 participants found that 6% of patients prescribed opioids for an acute musculoskeletal injury develop persistent opioid use [10]. The prevalence increased to 27% among injured patients receiving workers compensation benefits, Veterans Affairs claimants, or patient populations with high rates of concurrent substance use disorder [10]. One in five patients on chronic opioid therapy started with an opioid prescription from an orthopaedic surgeon [3]. It is important to establish which interventions for acute injuries are most likely to show a high net benefit, that is, good effectiveness for reducing pain and improving function, but a low risk of causing harm. This Cochrane review by Jones et al. [9] compared the benefits and harms of oral NSAIDs versus other pain medications like opioids for acute soft tissue injuries.

Upon Closer Inspection

This review included 20 randomized studies with 3305 patients, mostly with ankle or wrist sprains [9]. The authors found no difference between opioids and oral NSAIDs in terms of reducing pain in the short-term (moderate certainty evidence), nor did they find a difference in pain relief between NSAIDs and acetaminophen (high certainty evidence). However, the authors found a higher risk of gastrointestinal and neurological adverse events in the opioid group compared with NSAIDs (moderate certainty evidence), and slightly fewer gastrointestinal adverse effects with acetaminophen compared with NSAIDs (low certainty evidence). Additionally, they found NSAIDs may be superior to opioids for return to function after injury (low certainty evidence).

The results of this Cochrane review are consistent with another recent systematic review and network meta-analysis, which examined the management of acute non–lower back musculoskeletal injuries [2]. This 2020 review of 207 randomized clinical trials (for a total enrollment of 32,959 patients) explored all therapeutic options for non–lower back acute musculoskeletal injuries and found that topical NSAIDs, followed by oral NSAIDs and acetaminophen (with or without diclofenac), had the most favorable harm-benefit ratio. Compared with placebo, tramadol failed to achieve important benefits and opioids caused more adverse events. Both the Cochrane review and the network meta-analysis results demonstrate that opioids fail to achieve important benefits beyond interventions with less harm and provide compelling reasons to avoid prescribing opioids in the setting of acute non–lower back musculoskeletal injury [2].

One limitation of the trials included in the Cochrane review is that six of the 20 were at high risk of bias for selective outcome reporting, meaning that the studies failed to report prespecified outcomes or selectively reported harms. This is important because selective outcome reporting can make a treatment look more effective or less harmful than it is [6]. In particular, the authors identified that one of the included studies was industry-funded and reported fewer harms [7] than did other studies in the review. It is likely that not all adverse effects were captured, and therefore we do not have a full picture of the harms associated with these pain medications. Research on pain management in orthopaedics should prespecify all patient-important outcomes, with consideration of both benefits and harms, and fully report all prespecified outcomes.

Take-home Messages

This Cochrane review found no differences among oral NSAIDs, acetaminophen, and opioids in terms of reducing short-term pain from acute soft tissue injuries; however, opioids produced the greatest harms. Given these major findings, and that of another recent systematic review and network meta-analysis [2], orthopaedic surgeons should generally avoid prescribing opioids for patients with acute soft tissue injuries in favor of NSAIDs, acetaminophen, or nonpharmacological approaches like rest, ice, compression, and elevation (known as RICE). The Canadian Orthopaedic Association has released a position statement that strongly encourages orthopaedic surgeons to consider nonpharmacological strategies and nonopioid pain medications before opioids when managing acute pain [4].


1. Bridgman SA, Clement D, Downing A, Walley G, Phair I, Maffulli N. Population based epidemiology of ankle sprains attending accident and emergency units in the West Midlands of England, and a survey of UK practice for severe ankle sprains. Emerg Med J. 2003;20:508-510.
2. Busse JW, Sadeghirad B, Oparin Y, et al. Management of acute pain from non-low back musculoskeletal injuries: a systematic review and network meta-analysis of randomized trials. Ann Intern Med. Published online August 18, 2020. DOI: 10.7326/M19-3601.
3. Callinan CE, Neuman MD, Lacy KE, Gabison C, Ashburn MA. The initiation of chronic opioids: a survey of chronic pain patients. J Pain. 2017;18:360-365.
4. Canadian Orthopaedic Association. COA position statement: opioids and orthopaedic surgical practice. 2018. Available at: Accessed November 5, 2020.
5. Centers for Disease Control and Prevention. Data and statistics (WISQARS): cost of injury Reports. 2010. Available at: Accessed November 5, 2020.
6. Dal-Ré R, Marušić A. Prevention of selective outcome reporting: let us start from the beginning. Eur J Clin Pharmacol. 2016;72:1283-1288.
7. Dalton JD Jr, Schweinle JE. Randomized controlled noninferiority trial to compare extended release acetaminophen and ibuprofen for the treatment of ankle sprains. Ann Emerg Med. 2006;48:615-623.
8. Delgado MK, Huang Y, Meisel Z, et al. National variation in opioid prescribing and risk of prolonged use for opioid-naive patients treated in the emergency department for ankle sprains. Ann Emerg Med. 2018;72:389-400.e1.
9. Jones P, Lamdin R, Dalziel SR. Oral non-steroidal anti-inflammatory drugs versus other oral analgesic agents for acute soft tissue injury. Cochrane Database Syst Rev. 2020;8:CD007789.
10. Riva JJ, Noor ST, Wang L, et al. Predictors of prolonged opioid use after initial prescription for acute musculoskeletal injuries in adults: a systematic review and meta-analysis of observational studies. Ann Intern Med. 2020;173:721-729.
11. Sarcon AK, Heyrani N, Giza E, Kreulen C. Lateral ankle sprain and chronic ankle instability. Foot Ankle Orthop. 2019;4:1-10.
12. Valderrabano V, Hintermann B, Horisberger M, Fung TS. Ligamentous posttraumatic ankle osteoarthritis. Am J Sports Med. 2006;34:612-620.


© 2020 by the Association of Bone and Joint Surgeons