HQ Team
November 13, 2024: A team of international researchers has developed a non-addictive painkiller that remains inactive until it reaches sites of chronic pain. This innovative approach differs from traditional analgesics, which typically dull the nerves sending pain signals. Instead, the new medication directly addresses the underlying causes of chronic pain.
The compound, classified as a prodrug, is designed to activate through a chemical reaction with reactive oxygen species (ROS), such as hydrogen peroxide and peroxynitrite, which are present in higher concentrations at chronic pain sites. This mechanism allows the prodrug to circulate throughout the body without exerting effects until it arrives at the targeted area.
Professor Andrew Abell of the Department of Chemistry and the ARC Center of Excellence for Nanoscale BioPhotonics (CNBP) at the University of Adelaide, and the study’s co-corresponding author, highlighted the significance of their discovery: “Our team has created a targeted prodrug capable of relieving chronic pain during preclinical trials.” The researchers tested this prodrug on mouse models suffering from various forms of chronic pain, including diabetic neuropathy and osteoarthritis. Results showed that it effectively reversed hypersensitivity to touch and cold up to six months post-injury without inducing tolerance—an issue commonly associated with powerful opioids like morphine.
The prodrug’s effects were dose-dependent, but the researchers observed that repeated dosing maintained its analgesic effects.
Associate Professor Peter Grace from the University of Texas MD Anderson Cancer Center and a co-author of the study, noted that existing treatments for chronic pain only work for about one in six patients and primarily reduce nerve activity rather than addressing the root cause. The new prodrug represents a potential paradigm shift in treating chronic pain by targeting the molecules responsible for transmitting pain signals.
Chronic pain
Chronic pain affects millions of people worldwide. Pain management is a complex task with analgesics and non-nonsteroidal anti-inflammatory drugs (NSAIDs) being the first line of treatment. Severe pains may require opioids, which over long term can become addictive. This new approach of targeted activated delivery of painkillers can get rid of the opioid epidemic and dependency amongst a majority of patients.
The research has received funding from the US National Institutes of Health (NIH) through its Helping to End Addiction Long-term (HEAL) Initiative. The team plans to continue with preclinical trials to assess the prodrug’s effectiveness and safety before advancing to human trials. The chemical reaction utilized in this research is known as Baeyer-Villiger oxidation (BVO), which plays a crucial role in activating the prodrug within the body.
The study was published in the journal Nature Biotechnology.
