Publication explores use of liquid N2O for Sickle Cell pain relief

A new study from School of Dentistry researchers opens previously unknown opportunities for pain management in Sickle Cell Anemia.

Ana Oddo, researcher in the Division of Basic Sciences, spent twelve years as a physical therapist in Brazil before joining the School of Dentistry as a researcher working with Don Simone, PhD, professor and Chair of the Department of Diagnostic and Biological Sciences. So she’s no stranger to pain and how it can impact daily life.

“That experience gave me a deep desire to better understand pain and contribute to more precise solutions,” she explained. “Helping people has always been at the center of my life.”

Among other areas of focus, Simone’s lab explores the neural encoding of pain and hyperalgesia, including on patients with Sickle Cell Anemia. The team was approached by Hillhurst Biopharmaceuticals, a company that specializes in infusing gases into liquids, about an innovative new idea to treat Sickle Cell pain.

“With Sickle Cell Anemia, there is chronic pain, but our main concern was the pain from the vaso-occlusive crisis,” Simone explained. “These unpredictable events are the number one reason patients go to the hospital.” Once admitted to the hospital, patients are often given opioids to control the pain as they wait for the crisis to end. While en route to the hospital, many patients in France and the United Kingdom are given gaseous nitrous oxide to combat pain—a treatment that tends to be effective, but cannot be taken on one’s own at home due to the difficulties in proper dosage and inadvertent exposure.

That’s where Hillhurst came in: they proposed a product called HBI-201, a carbonated beverage with a precise dosage of nitrous oxide that can be provided to the patient to take at home as soon as a pain crisis begins. The researchers hope that taking this treatment at home, at the beginning of an event, can reduce pain, reduce the instance of opiate consumption and decrease the need for a hospital stay—in addition to reducing the side effects of gaseous nitrous oxide, including sedation.

“This is the first time nitrous oxide has been tested in a liquid form, in something as simple as a carbonated drink,” explained Oddo. “The possibility that patients could one day manage their pain with something so accessible is just incredible.”

Oddo and her team at Simone’s lab tested the effectiveness of the treatment on mice with Sickle Cell Anemia. The results were quite promising. “The drink had a great effect on reducing the pain produced by the crisis,” Simone explained. This included behavioral measures of pain and electrophysiology tests.

Oddo’s paper detailing the results of the study was pre-published in Haematologica in June 2025, alongside an editorial lauding the study and its importance in identifying methods of pain relief. Moving forward, Hillhurst will explore a series of toxicology studies before moving to a clinical trial, while Simone’s team will explore other possibilities for the use of the drink, including with burn patients, while also exploring the mechanism by which it reduces pain.

“We can help these patients not only alleviate their severe pain, but reduce the time they have to spend in the hospital,” Simone explained. “This is a different, clever way to deliver nitrous oxide in a manner that is effectively analgesic with minimal side effects.”

Oddo is thrilled to have been part of a study that has the potential to impact patients’ lives, and she knows this study is just the beginning.

“When I started this work, I never imagined I would focus on Sickle Cell Disease, but it turned out to be such a meaningful direction,” she reflected. “Pain crises are one of the most devastating aspects of this disease, and being able to contribute to research that could improve patients’ lives feels personal and purposeful. I hope that in the coming years, we’ll be able to move toward clinical trials and see how this approach will impact patients’ lives.”