Nordic Life Science 1
growing medical issue, with one in five people es
timated to have the condition. Add global concerns about the risky use of opioids tied to chronic pain, and the need for new painkilling treatments becomes even more urgent. New approaches to pain control could arise from a study in Science from Karolinska Institutet researchers. They found that cells that were previously thought to merely support pain-sensing neurons are directly involved in the pain response. The discovery is being called a new pain organ that could lead to novel therapeutic targets. Professor Patrik Ernfors, senior author on the paper, explains that his group was studying stem-like cells in the peripheral nervous system that produce Schwann cells. These cells usually support neurons rather than function in signalling. “We found strange-looking cells in the skin,” he says. “They formed a mesh-like network between the outer and inner skin layers and were closely linked to pain-initiating nerves.” The Ernfors group are experts in mouse genetics so to investigate the discovery, they turned to optogenetics, which is engineering neurons or other cells to contain light-sensitive ion channels. The researchers generated mice with these lightresponsive channels in the unusual skin Schwann cells. Shining a specific blue-light frequency on the skin of the modified mice activated the cells. In response, the mice reacted as though they had received a pain stimulus, for example by pulling back the limb exposed to the blue light. “We were very surprised,” Ernfors says. “For more than 100 years, everyone thought pain starts in nerves in the skin. Then we found Schwann cells connected to pain-initiating fibers and showed that activating these cells can produce pain.” With further optogenetics and electrophysiological experiments, the scientists showed that the newly identified painsensing Schwann cells are mechanosensitive. They contribute to the response to jabs, pokes, or excessive pressure. The Ernfors lab is now examining these Schwann cells more closely. They are using mouse genetics and a variety of other methods such electrophysiology and transcriptomics to identify the mechanism and molecules that allow the cells to detect pressure. he work could have clinical and pharmacological relevance, Ernfors says. His group is interested in finding out if the cells contribute to medical conditions such as chronic pain or neuropathies, for example that result from diabetes. “The ultimate goal is to find new strategies to treat chronic pain,” Ernfors says. “If we find something that could be useful, the rational way to take that idea into the clinic is with a startup or working with an established company.” NLS