A longitudinal study of subacute back pain (SBP) patients found that those who developed chronic back pain (SBPp) showed reduced gray matter density in brain regions such as the nucleus accumbens (NAc), insula, and left sensorimotor cortex. Functional connectivity between the NAc and prefrontal cortex predicted pain persistence, suggesting a causal role of corticostriatal circuits in the transition from acute to chronic pain. The study also showed that the NAc exhibited stronger positive functional connectivity with the medial prefrontal cortex (mPFC) in SBPp compared to those who recovered (SBPr). This connectivity was related to affective pain and persisted over time. The insula showed decreased negative connectivity with the dorsolateral prefrontal cortex and precuneus in SBPp, which was associated with pain intensity. These findings suggest that functional reorganization of the insula and sensorimotor areas is linked to gray matter changes and directly relates to pain persistence. The study also found that mPFC-NAc functional connectivity was a strong predictor of pain persistence, outperforming other parameters such as pain intensity and drug therapy. These results provide the first temporal profile of brain parameters during pain chronification, showing that SBPp patients exhibit distinct brain changes compared to healthy controls and those who recovered. The study highlights the role of the mesolimbic circuitry, particularly the NAc, in chronic pain and suggests that the mPFC-NAc circuitry is critical in the transition to chronic pain. The findings have implications for understanding the neural mechanisms underlying chronic pain and could inform future treatments.A longitudinal study of subacute back pain (SBP) patients found that those who developed chronic back pain (SBPp) showed reduced gray matter density in brain regions such as the nucleus accumbens (NAc), insula, and left sensorimotor cortex. Functional connectivity between the NAc and prefrontal cortex predicted pain persistence, suggesting a causal role of corticostriatal circuits in the transition from acute to chronic pain. The study also showed that the NAc exhibited stronger positive functional connectivity with the medial prefrontal cortex (mPFC) in SBPp compared to those who recovered (SBPr). This connectivity was related to affective pain and persisted over time. The insula showed decreased negative connectivity with the dorsolateral prefrontal cortex and precuneus in SBPp, which was associated with pain intensity. These findings suggest that functional reorganization of the insula and sensorimotor areas is linked to gray matter changes and directly relates to pain persistence. The study also found that mPFC-NAc functional connectivity was a strong predictor of pain persistence, outperforming other parameters such as pain intensity and drug therapy. These results provide the first temporal profile of brain parameters during pain chronification, showing that SBPp patients exhibit distinct brain changes compared to healthy controls and those who recovered. The study highlights the role of the mesolimbic circuitry, particularly the NAc, in chronic pain and suggests that the mPFC-NAc circuitry is critical in the transition to chronic pain. The findings have implications for understanding the neural mechanisms underlying chronic pain and could inform future treatments.