Capsaicin, the chemical that makes chili peppers spicy, has long been an ingredient in pain-relief creams, but scientists have only just discovered how the fiery molecule quiets sore nerves, muscles and joints.
Capsaicin turns on a protein that senses heat and starts an unexpected chain reaction that inhibits proteins that detect stretching of cell membranes, Tibor Rohacs of Rutgers New Jersey Medical School in Newark and colleagues report in the Feb. 10 Science Signaling. Researchers already knew capsaicin activates a heat-sensing protein called Trpv1. That’s why rubbing creams containing capsaicin on the skin produces a burning sensation.
Turning on Trpv1 also floods pain-sensing nerves with calcium, Rohacs and colleagues discovered. The calcium boost causes a drop in levels of two lipids, called phosphoinositides, in the nerve cells’ outer membranes. The lipid dip, in turn, silences two proteins called Piezo1 and Piezo2, which monitor membrane stretch. Those proteins are important for many biological processes, such as blood vessel constriction, touch and pain. Shutting down those stretch sensors blocks the pain signal.