HSS Study Evaluates Non-Opioid Pain Relief Following Orthopedic Surgery

A retrospective study presented at the 51st Annual Regional Anesthesiology and Acute Pain Medicine Meeting by investigators at Hospital for Special Surgery (HSS), the world's leading academic medical center focused on musculoskeletal health, found that a newly available non-opioid pain reliever was generally well tolerated by postoperative orthopedic surgery patients-an important step forward in advancing non-opioid pain management options.

The medication, suzetrigine (JOURNAVX®), was FDA-approved in January 2025 and became available at HSS in April 2025. It is the first non-opioid pain reliever released in more than 25 years.

Alexandra Sideris, PhD, Director of the Pain Prevention Research Center at HSS, and Faye Rim, MD, FAAPMR, a physiatrist and pain management specialist within the Department of Anesthesiology, Critical Care & Pain Management, co-led the study.

One advantage of the new medication is that it works differently from standard over-the-counter pain relievers and stronger medications like opioids.

"What's exciting about this new medication is that it is targeting pain signal on the nerves outside of the brain, so you're presumably getting to the acute pain source right at the time where that happens," Dr. Sideris said. "Early studies also suggest that it's devoid of those classical addictive properties that opioids have."

It's even more targeted than local anesthetics, which block pain messengers known as sodium channels. Instead, suzetrigine blocks just one sodium channel, Nav1.8, which means patients should experience fewer side effects and more targeted pain relief.

HSS was an early adopter in New York City to add suzetrigine to its formulary, and Dr. Rim was instrumental in bringing it to surgical patients. Patients managed by the Perioperative Pain Service often have complex needs that opioids alone may not be able to meet. Some patients may have other conditions that contraindicate the use of opioids. suzetrigine presents a novel, non-habit-forming option that can either replace or augment opioid use after surgery.

For this study, the team evaluated 103 HSS patients who took suzetrigine after undergoing a variety of surgical procedures, but primarily joint arthroplasty or spine surgery. Eight patients (7.8%) experienced at least one adverse reaction during admission, likely related to the drug, and ended up stopping the medication. The remaining 95 patients (92.2%) generally tolerated it well.

"The longer-term goal is to see if adding on suzetrigine actually decreases your need for opioids or if it is an effective option for patients undergoing major orthopedic surgery who cannot tolerate opioids," Dr. Sideris said.

Pain has historically been a challenging area for drug development, in part because preclinical models do not always predict human response.

"Unfortunately, many things that work in animals just haven't translated into humans, and it's been a quest to understand [why]," Dr. Sideris said.

But this drug's novel approach makes it an exciting advance in the field and one that HSS pain researchers were eager to capitalize on. This initial study gives a first look at how suzetrigine is tolerated in surgical patients at HSS, with an ongoing study in patients undergoing total hip replacements, and more research planned in patients knee, and spine surgery. Further studies will evaluate who may benefit from the medication the most, and who is more likely to require additional support. Currently, it is not a first-line medication, but Dr. Rim anticipates that will change as the drug becomes more widely available and additional evidence emerges on its efficacy in various surgical populations.

"We need to look more carefully at why certain patients may not do as well on this medication as we think they would," she said. "It's not a panacea, but it's definitely promising."

She added that HSS was an obvious choice for the medication's early adoption due to the institution's reputation for cutting-edge science and advanced care.

"HSS is known for being innovative and this falls in line with that," Dr. Rim said. "We want to try to utilize anything that's safe and effective within an arsenal to make sure patients recover well and become functional."