Persistent nociceptive inputs arising from peripheral tissues or/and nerve injuries cause maladaptive changes in neurons or neural circuits in the central nervous system, which further confer acute injury into chronic pain transitions (pain chronification) even after the injury is resolved. However, the critical brain regions and their neural mechanisms involved in this transition have not yet been elucidated. Here, we reveal an accumbal microcircuit that is essential for pain chronification. Notably, the increase of neuronal activity in the nucleus accumbens shell (NAcS) in the acute phase (<
7 days) and in core (NAcC) in the chronic phase (14-21 days) was detected in a neuropathic pain mouse model. Importantly, we demonstrated that the NAcS neuronal activation in the acute phase of injury was necessary and sufficient for the development of chronic neuropathic pain. This process was mediated by the accumbal dopamine D2 receptor-expressing neuronal microcircuit from NAcS to NAcC. Thus, our findings reveal an accumbal microcircuit mechanism for pain chronification and suggest that the early intervention targeting this microcircuit may provide a therapeutic approach to pain chronification.