Brainstem somatostatin-expressing cells control the emotional regulation of pain behavior

Upon threatening situations, animals exhibit a broad range of behavioral and autonomic responses. As such, a crucial adaptive response is the inhibition of pain to facilitate relevant defensive behaviors that promote survival. Whereas the structures and mechanisms involved in fear and pain behavior are well documented, little is known about the precise neuronal mechanisms mediating the emotional regulation of endogenous pain-suppression. Here we used a combination of behavioral, anatomical, optogenetic, and electrophysiological approaches to investigate the role of that somatostatin-expressing cells in the ventrolateral periaqueductal gray matter (SST+ vlPAG cells) in the control of analgesia induced during defensive states. Our data indicate that the optogenetic inhibition of SST+ vlPAG cells promotes analgesia irrespective of animals defensive state. In contrast, the optogenetic activation of long-range SST+ vlPAG cells that project to the rostral ventromedial medulla (RVM) abolishes the analgesia mediated by fear behavior. Together these results identify a novel circuit mechanism composed of long-range SST+ vlPAG cells projecting to the RVM that regulate analgesia elicited during defensive states.