Grant: Project Grant

Chronic pain affects as many as 1 in 5 people worldwide. As the population ages and modern medicine allows people to survive serious illness, the number of people affected by chronic pain is expected to rise to 1 in 3. Chronic pain can be debilitating, isolating, dehumanizing, and all too frequently, abuse of opioid painkillers can turn deadly (see the current crisis of fentanyl overdoses). Developing new tools to study pain and develop new avenues for analgesia is critical. Previous approaches to activate pain pathways used chemical, thermal, mechanical, or electrical stimulation. These stimuli lack spatial and/or temporal control and often involve invasive procedures. Our goal is to design novel genetic tools that ensure highly precise control on the activity of peripheral pain pathways, and therefore pain perception. Our data provide evidence that optical analgesia can be achieved in freely moving rodents without noxious stimuli or injury. Our approach relies on transgenic mice expressing light-sensitive proteins (opsins) into a specific group of genetically-identified sensory neurons called nociceptors. When exposed to light, light-sensitive proteins are activated, triggering or inhibiting the propagation of electric signals from the periphery to the brain, where pain is perceived. In this project, we propose the development of preclinical models in which pain can be modulated and remotely controlled without any tissue damage. The high sensitivity and specificity of our approach resulted in measurable behavioral responses of the transgenic transducer-expressing mice, following exposure to activators (nociception) or inhibitors (analgesia). Opto/chemogenetic stimulation or inhibition of the sensory pathways in vivo will allow us to investigate the critical role of specific neuronal populations in peripheral pain circuits, facilitating the development of analgesic drugs and gene therapy for the treatment of chronic pain.