FEARLESSPAIN

When facing danger, mammals display various fear responses among which an overlooked response is analgesia. Indeed, following fear conditioning, presentation of the conditioned stimulus lead to a reduction in pain sensitivity, a phenomenon known as fear conditioned analgesia (FCA). FCA results from the activation of descending pathways directly modulating pain processing in the dorsal horn of the spinal cord. However, to date the precise circuits and mechanisms involved in this phenomenon are largely unknown. Several brain regions, including the periaqueductal gray (PAG) are involved in fear and pain processing during FCA, yet the organization of PAG circuits and the mechanisms by which fear modulates pain sensitivity during FCA, remain unknown. In this proposal we address this fundamental question by a combination of state of the art in vivo extracellular and patch clamp recordings, anatomical tracing, optogenetic manipulations and behavioural approaches.