A research team at Duke University, together with colleagues, has discovered a potential new class of small-molecule drugs that simultaneously block two sought-after targets in the treatment of pain. These proof-of-concept experiments, published online on June 1, 2016 in Scientific Reports, could lead to the development of a new drug to treat conditions including skin irritation and itching, headaches, jaw pain, and abdominal pain stemming from the pancreas and colon. The open-access article is titled "Small Molecule Dual-Inhibitors of TRPV4 and TRPA1 for Attenuation of Inflammation and Pain." More than 100 million people suffer from chronic pain in the United States, according to a report from the Institute of Medicine, and new medicines are badly needed. "We are very pleased with what is a first chapter in a highly promising story," said Wolfgang Liedtke, M.D., Ph.D., a professor of neurology, anesthesiology, and neurobiology at Duke University School of Medicine, who treats patients with head and face pain and other sensory disorders. "We hope to be able to develop these compounds for clinical use in humans or animals." In the new study, the researchers initially aimed to develop more effective blockers of TRPV4 (image), a molecule their previous research had shown transmits skin irritation elicited by sunburn, and painful sensations coming from the head and face. Dr. Liedtke and his Duke collaborator Farshid Guilak used a prototype TRPV4 blocker in a 2009 study and then set out to develop more potent versions. Compared to the prototype, one of the new candidate drugs, called "16-8," worked 10 times more effectively in cells with active TRPV4 that are key for the development of osteoarthritis. It also worked well in another cell type involved in nerve cell injury, stroke, and epilepsy.
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