Photoswitch Molecule Controls Pain

A light-activated compound that resembles the anesthetic lidocaine might lead the way to future pain therapy, according to a report (Nat. Methods, DOI: 10.1038/nmeth.1897). Anesthetics typically suppress pain, but they take a while to wear off and are indiscriminate in which nerve cells they inhibit. Now, Richard H. Kramer of the University of California, Berkeley; Dirk Trauner of the University of Munich; and coworkers have developed a photoswitchable compound that targets specific neurons and can be turned on and off at will. They demonstrated that the lidocaine-like molecule, quaternary ammonium-azobenzene-quaternary ammonium (QAQ), blocks ion channels in pain-sensing nerve cells when in its trans form. After exposure to 380-nm light, QAQ switches to its cis form, unblocking the channels and allowing the neurons to transmit pain signals. The researchers regenerated trans-QAQ with 500-nm light. When applied to the eyes of mice along with the chili-pepper compound capsaicin, trans-QAQ slipped into the rodents’ nerve cells through the protein receptor TRPV1 and lessened the critters’ response to pain. Fiber-optic systems will be needed to use compounds like QAQ inside humans, the scientists say, but meanwhile these photoswitches can help map pain circuitry in the body.