Creating a New Class of Painkillers

Painkillers - “analgesics,” to use the two dollar word – come in a variety of types. You certainly know about non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin, and you likely have been prescribed an opioid, such as oxycodone, once or twice in your life. Less common varieties of analgesics include Flupirtine, a particularly strong pain-reliever and muscle relaxant more popular in Europe for migraine relief, and COX-2 inhibitors, which have fallen out of favor due to their unpleasant tendency to increase the risk of cardiovascular events.

All told, there's really not a lot of flavors from which to choose, so the discovery of a potential new class of painkiller is happy news. And that is just what a research team from Duke University recently – potentially – discovered.

The data from the researchers' proof-of-concept experiments were published June 1 in Scientific Reports.  The trials 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.

"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."

The intent of the experiments initially was to create a more effective blocker of the molecule TRPV4 which transmits skin irritation elicited by sunburn, and painful sensations coming from the head and face. They were successful in that they created a drug they called 16-8 which 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.

But the serendipitous moment occurred when the teamdiscovered that the new drug also blocked TRPA1, which is a promising target in pain and itch research. The drug 16-8 also killed pain in living animals, including abdominal aches in mice with pancreas inflammation. “So-called pancreatitis is extremely painful and difficult to treat, and new cases are on the rise globally,” said study co-author Rodger Liddle, M.D., of the Duke University School of Medicine and a member of the Duke Institute for Brain Sciences.

Liedtke sees potential for the 16-8 drug to treat osteoarthritis and other types of joint pain as well as head, face and jaw pain. In general, it might also treat aches radiating from internal organs or resulting from nerve cell injury.