Mapping Cortical Integration of Sensory and Affective Pain Pathways

Pain is an integrated sensory and affective experience. Cortical mechanisms of sensory and affective integration, however, remain poorly defined. Here, we investigate the projection from the primary somatosensory cortex (S1), which encodes the sensory pain information, to the anterior cingulate cortex (ACC), a key area for processing pain affect, in freely behaving rats. By using a combination of optogenetics, in vivo electrophysiology, and machine learning analysis, we find that a subset of neurons in the ACC receives S1 inputs, and activation of the S1 axon terminals increases the response to noxious stimuli in ACC neurons. Chronic pain enhances this cortico-cortical connection, as manifested by an increased number of ACC neurons that respond to S1 inputs and the magnified contribution of these neurons to the nociceptive response in the ACC. Furthermore, modulation of this S1→ACC projection regulates aversive responses to pain. Our results thus define a cortical circuit that plays a potentially important role in integrating sensory and affective pain signals. •Anterior cingulate cortex (ACC) receives inputs from the somatosensory cortex (S1)•Activation of the S1 inputs increases the nociceptive response in the ACC•This cortico-cortical projection regulates pain-aversive behaviors•Chronic pain enhances the connection between the S1 and the ACC Singh et al. reveal that neurons from the anterior cingulate cortex (ACC) receive inputs from the primary somatosensory cortex (S1) and that the activation of these inputs increases the nociceptive response in the ACC and pain-aversive behaviors. Chronic pain, meanwhile, enhances the nociceptive connection between the S1 and the ACC.