CHRONIC INFLAMMATORY PAIN ALTERS REWARD-EVOKED DOPAMINE DYNAMICS IN THE NUCLEUS ACCUMBENS

Clinical evidence indicates that between 32% and 56% of people experiencing chronic pain are at risk of developing a mood disorder, however the mechanisms underlying this association remain unknown. We aim to investigate how chronic inflammatory pain affects anxiety, despair and anhedonia, and to examine its impact on dopamine dynamics in the Nucleus Accumbens. Male mice were stereotaxically injected with the dopamine sensor dLight1.3 into the Nucleus Accumbens. After 3 weeks of recovery, animals were trained to self-administer sugar pellets and subsequently injected with 30 mL of the inflammatory agent Complete Freund’s Adjuvant (CFA) or saline into the hind paw. Progressive ratio testing was conducted at 0, 4, 7 and 14 days after injection while recording dopamine dynamics with fiber photometry. At day 16, a battery of behavioral tests was performed to assess anxiety-like behavior (elevated plus maze,EPM), anhedonia (2 bottle choice) and despair (tail suspension,TS). At the end of the experiments, all animals were sacrificed and perfused, and brains were collected for the analysis of neuroactivation paterns with c-fos. CFA-treated mice obtained less rewards and showed fewer responses during self-administration tasks compared to controls. Behavioral testing suggested increased despair-like behavior in inflamed mice, with no significant differences in other tests. Histological analyses showed distinct activation patterns on pain and mood processing areas between control and inflamed animals. These findings confirm chronic pain disrupts the reward system processing and promotes maladaptive mood-related behaviours. Moreover, they highlight specific areas that may act as integrative hubs for pain and affective states.