New oral pain medication may reduce the need for opioids after surgery

Clinical takeaway: Effective nonopioid options for acute pain remain a major unmet need. In this phase 2b trial, an investigational oral pain medication that blocks pain signals in peripheral nerves reduced postoperative pain, and the higher dose also decreased opioid rescue medication use. If confirmed in phase 3 studies, this approach could expand oral analgesic options while reducing opioid exposure.

Postoperative pain is still commonly managed with opioids despite concerns about adverse effects and the risk of persistent opioid use. New analgesics that target pain signaling outside the central nervous system could offer effective pain control with fewer opioid-related complications.

In this phase 2b trial, 343 patients with moderate-to-severe pain after abdominoplasty were randomized to receive one of two doses of an investigational oral nonopioid pain medication, hydrocodone-acetaminophen, or placebo for 48 hours.

Both doses of the investigational medication significantly reduced pain compared with placebo. Pain relief with the higher-dose regimen was numerically greater than that seen with hydrocodone-acetaminophen, although the study was not designed to compare the active treatments directly.

The higher-dose regimen also reduced opioid rescue medication use. Patients receiving the higher dose required an average of 11.0 morphine milligram equivalents of rescue opioids compared with 18.4 among placebo recipients, and 52% required no opioid rescue medication versus 22% in the placebo group.

Adverse events were generally infrequent. Compared with placebo, the higher-dose regimen was associated with higher rates of pyrexia (7% vs. 2%) and presyncope (6% vs. 1%).

NaV1.8 is a sodium channel found primarily on peripheral pain-sensing nerves. By selectively blocking this target, the drug is designed to reduce pain without acting on the brain or spinal cord like opioids. Although larger trials are needed, the results suggest this approach could introduce a new class of oral nonopioid analgesics for acute postoperative pain.

Source: Singla N, et al. (2026 Jul 29) N Engl J Med. Phase 2b trial of a NaV1.8 inhibitor for acute pain