Scientists turn pain on and off, with a beam of light.
Some of the mice squeaked in agony when researchers aimed a blue light at their paws. Other mice felt nothing at all when zapped with a laser.
In the latest demonstration of optogenetics, a versatile but complex technology for controlling nerve cells, a research team at Stanford University has sketched out how patients afflicted by chronic pain might one day find relief: simply by pressing a bright flashlight to their skin.
“Patients could be given their own ability to create a pain block on demand,” says Michael Kaplitt, a neurosurgeon and chief scientific officer of Circuit Therapeutics, a three-year-old Palo Alto, California, biotechnology startup now working on a pain treatment along with the Stanford scientists.
Optogenetics is a breakthrough technology that is giving scientists precise control over what animals feel, how they behave, and even what they think. It relies on modifying the DNA of neurons so that they send signals—or are blocked from firing—in response to light (see “Brain Control”). The technique was invented nine years ago in the laboratory of Karl Deisseroth, one of Circuit’s cofounders and an author of the new pain study.
So far, the most striking use of optogenetics has been to produce effects directly inside animals’ brains, using light piped in with an implanted fiber-optic cable. In an earlier study, Deisseroth’s group made mice feel fear or become fearless (“An On-Off Switch for Anxiety”).
Circuit, which now has 47 employees, is working to engineer light sources and perfect genetic tools to take advantage of optogenetics. Kaplitt says that in addition to its research on pain, the company hopes to figure out how to treat serious psychiatric disease with implants that carry light into the brain.
But controlling nerves outside the brain could prove easier. The sensitive nerve endings, or nociceptors, that fire off warnings in response to heat or pressure lie only two hair-breadths beneath human skin, and could be controlled by a bright handheld light. “We have engineers thinking about what that kind of device would look like,” says Kaplitt. “Pain is a perception. So the idea is to stop the perception of it.”
In the Stanford group’s latest work, published in the journal Nature Biotechnology, they first used gene therapy to install light-sensitive molecules into the nerve endings in the skin of mice. Each animal was then placed into a small plexiglass chamber with a transparent floor.
When the researchers shined blue light through the floor, the mice “flinched,” cried out, or “engaged in prolonged paw licking,” all signs of pain. The team could also block sensation. In those tests, mice that were bathed in yellow light designed to block nerve impulses weren’t greatly bothered by a band pinching their leg. When the researchers pointed hot lasers at their paws, they were slow to react.