A combination of two drugs can selectively block pain-sensing neurons in rats without impairing movement or other sensations such as touch, according to a study published in the Oct. 4 issue of Nature.
The study, conducted by National Institutes of Health–(NIH-) supported investigators, used a combination of capsaicin (the substance that makes chili peppers hot) and a drug called QX-314. Although QX-314 is a lidocaine derivative, it cannot get through cell membranes by itself to block the electric currents in nerve cells. Capsaicin, however, opens large pores called TRPV1 channels that are found only within the cell membrane of pain-sensing neurons. When these channels are opened by capsaicin, QX-314 can pass through and selectively block the cells’ activity. In contrast, most pain relievers used for surgical procedures block activity in all types of neurons, which can cause numbness, paralysis and other nervous system disturbances.
The research team, led by Clifford J. Woolf, MD, PhD, of Massachusetts General Hospital, Boston, and Harvard Medical School, Boston, and Bruce Bean, PhD, of Harvard Medical School, tested the capsaicin and QX-314 combination in neurons isolated in Petri dishes and found that it blocked pain-sensing neurons without affecting other nerve cells. They then injected the drugs into the paws of rats and found that the treated animals could tolerate much more heat than usual. They also injected the combination into the rats’ sciatic nerve that runs down the hind leg. The treated rats did not show any signs of pain, and five of the six animals continued to move and behave normally. The drug combination took half an hour to fully block pain in the rats. Once it began, however, the pain relief lasted for several hours.
"This finding shows that a specific combination of two molecules can block only pain-related neurons. It holds the promise of major future breakthroughs for the millions of persons who suffer with disabling pain," says Story C. Landis, PhD, director of the National Institute of Neurological Disorders and Stroke at the NIH, which funded the research along with the National Institute of Dental and Craniofacial Research and the National Institute of General Medical Sciences.
