Project 1 of this P20 center research plan will focus on human subjects to examine the interaction of functional and structural circuitry alterations in chronic pain and opioid addiction. It will specifically examine two separate cohorts of subjects for test/retest purposes, each cohort comprising five groups of human subjects who represent a continuum between opioid addiction and chronic pain. These five groups will include: (i) individuals with addiction to opiates who have no history of chronic pain, (ii) individuals with chronic pain who have developed addictive behaviors toward opioid analgesics, (iii) individuals with chronic pain who have treatment based exposure to analgesics but no addiction behavior, and (iv) individuals with chronic pain who have no exposure to analgesics. A fifth group of healthy controls (v) with neither chronic pain nor addiction to opioid analgesics will serve as a baseline control group for the four clinical groups (i) - (iv). Across these groups of subjects in each of the two cohorts, we will compare and contrast BOLD signal measured by functional MRI in a limited set of reward/aversion brain regions that have been implicated in both addiction and chronic pain, such as the nucleus accumbens, amygdala/hippocampus, ventral tegmentum, and regions of the prefrontal cortex. Neural function will be assessed against morphometric and topological measures across the five groups of human subjects. We hypothesize that opioid addiction and chronic pain will modulate reward/aversion behavior and function in apriori regions in a convergent direction and share phenotypic features, correlating with altered morphometry measures. Across three specific aims, we will test if mildly rewarding or aversive stimuli elicit attenuated responses across the four clinical groups with addiction and/or chronic pain, and whether strongly aversive stimuli elicit hypersensitive responses. Aim 1 will assess differences in reward processing using a keypress paradigm testing judgment and decisionmaking around relative preference for drug cues or phenotypic features of addiction. Aim 2 will compare and contrast physical and psychological aversion across the five human groups using thermal pain and monetary losses in a game of chance. Aim 3 will determine if brain structural/topological alterations in addiction are also found in chronic pain, and assess the interactions of structural/topological differences with symptom severity and functional differences from Aims 1 and 2.