The Neural Basis of Pain Unpleasantness and Its Modulation By Opioids

Pain is a multidimensional experience with sensory and emotional components. Emotions associated with the experience of pain are characterized by their aversive and unpleasant quality. It remains unknown how the brain attributes this aversive quality to the emotionally inert pain information transmitted by the spinal cord. Resolving the neural mechanisms underlying the emotional component of pain could lead to the development of a novel generation of painkillers that will eliminate pain unpleasantness. To this aim, we use time-lapse in vivo calcium imaging in mice experiencing pain, to identify the principles of pain representation within brain networks encoding emotions. We also manipulate neural activity in these networks, and assess the behavioral consequences on the sensory and affective components of pain. We found that a diverse array of painful experiences are encoded in a discrete neural ensemble of the basolateral amygdala, a region of the temporal lobe involved in emotions. Silencing of this ensemble specifically alleviates pain emotional behaviors, without altering the sensory detection of noxious stimuli. These results identify a neural representation of pain in the amygdala that is necessary for the instantiation of the negative emotional qualities of pain. We also investigate the functional organization of the endogenous opioid system.