Despite the abuse potential of opioid drugs, they have long been the best option for patients suffering from severe pain. The drugs interact with receptors on brain cells to tamp down the body’s pain response. But now, neuroscientists at Washington University School of Medicine in St. Louis have found a way to activate opioid receptors with light.
In a test tube, the scientists melded the light-sensing protein rhodopsin to key parts of opioid receptors to activate receptor pathways using light. They also influenced the behavior of mice by injecting the receptors into the brain, using light instead of drugs to stimulate a reward response.
Their findings are published online April 30 in the journal Neuron.
The eventual hope is to develop ways to use light to relieve pain, a line of discovery that also could lead to better pain-killing drugs with fewer side effects.
“It’s conceivable that with much more research we could develop ways to use light to relieve pain without a patient needing to take a pain-killing drug with side effects,” said first author Edward R. Siuda, a graduate student in the laboratory of Michael R. Bruchas, PhD, an assistant professor of anesthesiology and of neurobiology.
But before that’s possible, the researchers are attempting to learn the most effective ways to activate and deactivate the opioid receptor’s pathways in brain cells. Bruchas, the study’s principal investigator, explained that working with light rather than pain-killing drugs makes it much easier to understand how the receptors function within the complex array of cells and circuits in the brain and spinal cord.
“It’s been difficult to determine exactly how opioid receptors work because they have multiple functions in the body,” Bruchas explained. “These receptors interact with pain-killing drugs called opiates, but they also are involved in breathing, are found in the gastrointestinal tract and play a role in the reward response.”
So the researchers sought a way to limit opioid receptors to performing a single task at a time, and it turned out to be almost as easy as flipping on a light switch, according to Bruchas, Siuda and their collaborators, including co-first author Bryan A. Copits, PhD, a postdoctoral research scholar in the laboratory of Robert W. Gereau, IV, PhD, the Dr. Seymour and Rose T. Brown Professor of Anesthesiology.
By combining the rhodopsin protein, which senses light in the eye’s retina, with a specific type of opioid receptor called a Mu opioid receptor, the researchers were able to build a receptor that responds to light in exactly the same way that standard opioid receptors respond to pain-killing drugs.
When an opioid receptor is exposed to a pain-killing drug, it initiates activity in specific chemical pathways in the brain and spinal cord. And when the researchers shone light on the receptors that contained rhodopsin, the same cellular pathways were activated.
In a test tube and in cells, Siuda exposed the receptors to light and then watched as they released the same chemicals that standard opioid receptors release. Then, in mice, the researchers implanted a light-emitting diode device the size of a human hair into a brain region linked to the reward response. They injected the light-sensing receptors they had genetically manufactured into the same brain region. Neurons in that part of the brain release chemicals such as dopamine that create feelings of euphoria.