Recent neuroimaging studies suggest that the brain adapts with pain, as well as imparts risk for developing chronic pain. Within this context, we revisit the concepts for nociception, acute and chronic pain, and nega-tive moods relative to behavior selection. We redeﬁne nociception as the mechanism protecting the organism from injury, while acute pain as failure of avoidant behavior, and a mesolimbic threshold process that gates the transformation of nociceptive activity to conscious pain. Adaptations in this threshold process are envi-sioned to be critical for development of chronic pain. We deconstruct chronic pain into four distinct phases, each with speciﬁc mechanisms, and outline current state of knowledge regarding these mechanisms: the limbic brain imparting risk, and the mesolimbic learning processes reorganizing the neocortex into a chronic pain state. Moreover, pain and negative moods are envisioned as a continuum of aversive behavioral learning, which enhance survival by protecting against threats.