Less is more in relieving musculoskeletal pain in children

In children with acute nonoperative musculoskeletal injury, treatment with ibuprofen alone appears adequate for relieving pain, with the addition of acetaminophen or hydromorphone yielding no additional analgesic effect, as shown in two No OUCH randomized clinical trials.

In pooled analyses, the primary outcome of self-reported verbal numerical rating scale (vNRS) pain at 60 min following medication administration did not significantly differ across the three treatment groups: ibuprofen plus hydromorphone, ibuprofen plus hydromorphone, and ibuprofen only (4.8, 4.6, and 4.6, respectively; p=0.78), reported first study author Dr Samina Ali from the University of Alberta in Edmonton, Alberta, Canada, and colleagues. [JAMA 2026;335:863-873]

More importantly, adverse events (AEs) occurred four times more frequently among children who received ibuprofen plus hydromorphone than among those who received ibuprofen plus acetaminophen or ibuprofen only (28.2 percent, 6.1 percent, and 5.8 percent, respectively), Ali and colleagues noted.

The most common AEs were somnolence, fatigue, dizziness, abdominal pain, nausea, and vomiting. All AEs in the ibuprofen and ibuprofen plus acetaminophen groups were rated as mild in severity. In the ibuprofen plus hydromorphone group, 80.4 percent of AEs were rated as mild, while 19.4 percent were rated as moderate. There were no cases of serious AEs or deaths.

Avoiding opioids

“These trials provide some of the strongest evidence to date to guide management of one of the most common paediatric pain presentations in the ED setting,” wrote Drs Jessica Calihan from Harvard Medical School, Boston, Massachusetts, US; Tori Sutherland from the University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, US; and Scott Hadland from Harvard Medical School, in an accompanying editorial. [JAMA 2026;335:856-858]

“For clinicians, the data provide reassurance that avoiding opioids for acute musculoskeletal pain is not undertreatment for most youth, but likely best practice. For families, the findings offer clarity: their child would likely not benefit from something stronger than ibuprofen to achieve adequate pain relief—and, in fact, their child might experience unnecessary central nervous system or gastrointestinal adverse effects from an opioid,” according to Calihan and colleagues.

They highlighted why hydromorphone might have been expected to provide superior analgesic benefit, saying that hydromorphone has approximately five times greater potency and penetrates the central nervous system more rapidly compared with morphine. “Yet, the study by Ali [and colleagues] showed that this theoretical advantage did not translate into better outcomes in youth with nonoperative musculoskeletal pain.”

AAP guidelines

Guidelines released by the American Academy of Pediatrics (AAP) in late 2024 recommend the use of nonopioid medications (ie, nonsteroidal anti-inflammatory drugs and acetaminophen), along with nonpharmacologic interventions (eg, the use of cold or heat, careful positioning of an injury, splinting, and relaxation techniques), for treating acute pain. [Pediatrics 2024;e2024068752]

In cases where an opioid prescription is needed, the AAP guidelines state that clinicians prescribe the lowest effective dose of an immediate-release formulation for the shortest possible duration (generally 5 days or fewer). Additionally, clinicians should co-prescribe the opioid antagonist naloxone while educating families or caregivers on recognizing and responding to overdose, as well as on the importance of administering every dose directly and having a clear plan for safe disposal of unused medications (eg, in-office drop-off or a local medication take-back site).

Consistent with the guidelines and the findings from the No OUCH trials, “the goal is not to eliminate opioid use entirely, but to ensure that when clinicians provide an opioid, they do so judiciously and safely,” according to Calihan and colleagues.

“Compassionate and appropriate pain management is a professional obligation—one that requires clinicians to avoid the harms of untreated pain while also minimizing the potential harms of opioid exposure,” they said.

No OUCH trials

No OUCH consisted of an opioid and a nonopioid trial, conducted simultaneously at six university-affiliated, tertiary care Canadian paediatric emergency departments. Ali and colleagues enrolled 699 children aged 6–17 years (mean 11.5 years, 47.4 percent female) presenting with a nonoperative acute limb injury (<24 hours) and a vNRS pain score of at least five (mean 6.4).

In the opioid trial, the children were randomly assigned to receive a single oral dose of ibuprofen plus hydromorphone (n=110), ibuprofen plus acetaminophen (n=70), or ibuprofen alone (n=69). In the nonopioid trial, children were randomized to treatment with a single oral dose of ibuprofen plus acetaminophen (n=225) or ibuprofen alone (n=225). Across all treatment groups, ibuprofen was dosed at 10 mg/kg (maximum of 600 mg). The acetaminophen dose was 15 mg/kg (maximum of 1,000 mg), and the hydromorphone dose was 0.05 mg/kg (maximum of 5 mg).

Pooled results for the secondary efficacy outcomes were similar across the three treatment groups. The percentage of children who achieved mild pain (vNRS score <3) was 23.4 percent in the ibuprofen plus hydromorphone group, 19.9 percent in the ibuprofen plus acetaminophen group, and 19.3 percent in the ibuprofen group (p=0.95). There were 44.9 percent, 47 percent, and 48.7 percent of children in the respective groups who reported a reduction of at least 2 points on the vNRS at 60 min. Length of ED stay averaged 2.8 h for the three groups. None of the children required rescue analgesia within 60 min after study drug administration.