New Anesthetic Avoids Common Side Effects

Capsaicin—the ingredient that gives chili peppers their heat—turns the lidocaine derivative QX-314 into an injectable local anesthetic that blocks pain without causing the paralysis or numbness associated with most local anesthetics. This activity profile could be useful in childbirth, treatment of some forms of chronic pain, and other circumstances in which a patient wants to maintain motor capabilities as well as awareness of nonpainful sensations.

The compound blend works by blocking sodium ion channels in nerves that sense pain, thereby preventing the nerves from transmitting pain signals to the brain, according to neurobiologist Bruce P. Bean of Harvard Medical School, anesthesia research chair Clifford J. Woolf of Massachusetts General Hospital, and Woolf's postdoc Alexander M. Binshtok (Nature 2007, 449, 607).

As a result of the findings, QX-314, "which was until now just an exotic reagent used by ion-channel biologists, will be the focus of a new effort in the search for better analgesics," comments neuroscientist Edwin W. McCleskey, scientific officer at Howard Hughes Medical Institute (Nature 2007, 449, 545).

Most local anesthetics move into nerve cells by taking on an uncharged form that can readily pass through the cells' oily lipid membrane. The anesthetics then plug the cells' sodium channels from the inside. This entry method is nonselective, however, so these anesthetics can enter nerve cells that control functions unrelated to pain, such as movement.

By itself, QX-314 is unable to get through the lipid membrane of nerve cells because it is positively charged. But tests in rats show that capsaicin provides QX-314 an entr??e to the cells by opening their so-called TRPV1 ion channels. QX-314 passes through these channels into the cells and then plugs the sodium channels. Because the TRPV1 ion channels are found only on pain-sensing nerve cells, QX-314 activity is limited to these cells alone.

"We've introduced a local anesthetic selectively into specific populations of neurons," Bean says. "Now we can block the activity of pain-sensing neurons without disrupting other kinds of neurons that control movements or nonpainful sensations."