NIH Scientists Report Breakthrough Plant-Derived Therapy Reduces Intractable Cancer Pain by 38%

National Institutes of Health查看公司主页 scientists have achieved a significant breakthrough in cancer pain management with the first-in-human clinical trial of resiniferatoxin查看药品详情 (RTX查看药品详情), a plant-derived therapy that demonstrated remarkable efficacy in patients with intractable cancer pain. The study showed that a single injection of RTX into the lumbar cerebrospinal fluid reduced patients' worst pain intensity by 38% and decreased their opioid use by 57%.

Targeting the Most Vulnerable Cancer Patients

The trial enrolled research participants with terminal end-stage cancer who represented the 15% of cancer patients unable to find pain relief from standard care interventions, including vast quantities of opiates. These patients experienced immediate and durable relief following a single RTX查看药品详情 injection, with significant improvements in quality of life.

"The effects are immediate," said Andrew Mannes, M.D., lead study author and chief of the NIH查看公司主页 Clinical Center Department of Perioperative Medicine. "This is a potential new therapy from a new family of drugs that gives people with severe cancer pain an opportunity to return some normality to their lives."

Following treatment, patients no longer needed to spend significant periods being sedated with opioids and were able to reengage with their family, friends and communities.

Selective Mechanism of Action

RTX查看药品详情 operates through a highly selective mechanism that distinguishes it from existing pain management approaches. The therapy prevents pain signals from reaching the brain by inactivating a specific sub-group of nerve fibers that transmit heat and pain signals from damaged tissue. RTX functions as an activator of the transient receptor potential vanilloid 1 (TRPV1 (搜索)搜索该靶点) ion channel and represents a super-potent equivalent of capsaicin, the active molecule in hot peppers.

"Basically, RTX查看药品详情 cuts the pain-specific wires connecting the body to the spinal cord, but leaves many other sensations intact," explained senior study author Michael Iadarola, PhD, a senior research scientist in the NIH查看公司主页 Clinical Center Department of Perioperative Medicine. "These TRPV1 (搜索)搜索该靶点 neurons are really the most important population of neurons that you want to target for effective pain relief."

The ability of RTX查看药品详情 to open the channel pore in TRPV1 (搜索)搜索该靶点 allows an overload of calcium to flood into the nerve fiber and block its ability to transmit pain signals. Unlike other current approaches that use heat, cold, chemicals, or surgery to non-selectively interrupt nerves, RTX targets specific sensory pathways while preserving touch, pin prick, pressure, muscle position sense (proprioception), and motor function.

Non-Addictive Alternative

RTX查看药品详情 offers a crucial advantage over current pain management strategies as it is not addictive and doesn't cause a high. "What makes this unique from all the other things that are out there is this is so highly selective," Mannes said. "The only thing it seems to take out is heat sensation and pain."

Plant Origins and Development

RTX查看药品详情 is derived from the Euphorbia resinifera plant, a cactus-like plant native to North Africa. Euphorbia extract has been known for 2,000 years to contain an "irritant" substance. NIH查看公司主页 scientists identified how to use this compound for patients through basic research on living cells observed through a microscope. Adding RTX to TRPV1 (搜索)搜索该靶点-containing cells caused a visible calcium overload, which Iadarola and Mannes eventually translated into the early-stage human clinical trial.

Broader Therapeutic Potential

The NIH查看公司主页 scientists believe RTX查看药品详情 has potential to treat many other pain conditions beyond cancer pain, including chronic pain from nerve injuries called neuromas, post-surgical pain, trigeminal neuralgia (a facial pain condition), and chronic oral inflammatory problems following head and neck radiation therapy.

"Targeting specific nerves brings many pain disorders into range of RTX查看药品详情 and allows physicians to tailor the treatment to the patient's pain problem. This interventional approach is a simple path to personalized pain medicine," Iadarola said.

Next Steps

The research team plans additional, larger clinical trials to move RTX查看药品详情 toward eventual approval by the U.S. Food and Drug Administration and clinical availability. This research was supported by the Intramural Research Program of the NIH查看公司主页 Clinical Center and NIH's National Institute of Neurological Disorders and Stroke.