Branco Weiss Fellow Since
2022
Research Category
Neuroscience
Research Location
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, USA
Background
Chronic pain afflicts a fifth of the population, but effective treatments are few. We urgently need new approaches to develop better painkillers. Despite the ever-increasing burden of chronic pain on our society, progress has been slow in investigating the emotional dimension of pain and its modulation by the brain. When an injured animal encounters a predator, ongoing pain is suppressed by the brain to enable the successful execution of defensive behaviors essential for survival. By identifying and manipulating the evolutionarily-conserved pathways for shutting off pain, it may be possible to identify new molecular targets to treat pain where it hurts – in the brain.
Details of Research
Animals must prioritize between competing threats to guide behavior. Pain is suppressed in the face of danger because attending to injury would disrupt other actions more essential to survival. Since the first predators appeared half a billion years ago, arms races between predator and prey species have been key drivers of brain evolution. Together with the observation that predators preferentially target injured animals, this leads to the hypothesis that pain suppression evolved during predator-prey conflicts to increase the chance of survival. Dr. Donald Iain MacDonald therefore wants to use the ‘natural’ stimulus for pain suppression – predatory threat – to reveal evolutionary-conserved circuits that turn off pain in the mouse brain. Combining quantitative behavior, activity-dependent circuit manipulations, in vivo imaging and molecular analysis, Dr. MacDonald will identify and characterize predator-activated neurons that inhibit pain. Ultimately, he aims to use predator exposure as a gateway to find new cellular and molecular targets for pain relief.
