Rethinking Pain: Uncovering the genes for pain resilience

We are all familiar with the sensation of pain, but have you ever wondered why some people experience pain more vividly than others? For years, perplexed researchers have documented individual differences in pain tolerance to no avail. In a paper recently published in the Journal of Neuroscience, Malgorzata Mis, a postdoctoral associate in the Department of Neurology at Yale University, working with a team of researchers from the Yale School of Medicine and Veterans Affairs Connecticut Healthcare System, has taken the first steps towards identifying the genes involved in pain perception. 

The researchers analyzed a mother and son with inherited erythromelalgia, a disease caused by a mutation within a gene that kindles pain and burning sensations when expressed in the nervous system. Despite having the same mutation, the mother and son reported different levels of pains in a previous study. “The son reported over one-hundred nightly awakenings due to his mutation within a fifteen-day period, while the mother reported only one awakening,” Mis said.

To further study this disparity, the research team grew sensory neurons derived from the mother’s and son’s stem cells in a laboratory dish. Using whole exome sequencing coupled with computer-aided dynamic clamp, a method that merges the visualization of live neurons with computational models, the researchers were able to identify a variation in the mother’s potassium channel encoded by the KCNQ2 gene, which ultimately led to her resilience to pain. The team is optimistic about implementing these new genetic methods that will guide them toward better treatments for pain.