Overlapping neuroanatomical and functional circuitry involved in chronic pain and opioid misuse. Neuroinflammation occurs in mesolimbic circuitry important for reward and motivation. A. Risk factors identified for opioid misuse in chronic pain populations. B. Chronic pain and chronic opioids induce neuroinflammation in brain regions associated with sensory and affective components. Red solid line arrows indicate sensory pain pathways. Red double line arrows indicate affective component of pain pathways. Purple brain regions denote where changes in neuroinflammation was detected by protein or mRNA of Iba-1 (a marker of microglia), cd11b (marker of microglia) or pro-inflammatory cytokines. Many structures overlap with opioid reward/reinforcement and negative affect/aversion such as the anterior cingulate cortex (ACC), prefrontal cortex (PFC), insula, thalamus, nucleus accumbens (NAc), and amygdala (AMY). C. Schematic cartoon of the central role neuroinflammation has in producing dysregulation of dopaminergic circuitry in many psychiatric disorders including chronic opioid use, chronic pain and depression. Note in panels B and C, the absence of purple shading does not reflect that neuroinflammation is absent in these structures, but rather many of these regions have not been examined. DS: dorsal striatum, OFC: orbitofrontal cortex, PAG: periaqueductal grey, PB: parabrachial nucleus, S1: primary somatosensory cortex, S2: secondary somatosensory cortex, VTA: ventral tegmental area.