Recently, research has focused extensively on the peripheral mechanisms that contribute to pain chronification, but our knowledge on the involvement of different brain regions remains limited. The Nucleus Accumbens (NAc) is a central hub for reward-related processes, with its interneurons having significant potential to control NAc output signals. However, their involvement in the chronification of pain has not been investigated until now.In this study, we performed patch-clamp recordings of cholinergic interneurons (ChIs) and GABAergic interneurons positive for parvalbumin (PV-GaIs) and somatostatin (SOM-GaIs) in the NAc shell and core subregions of respective cre-reporter mice seven days after spared nerve injury (SNI).We found that all interneuron types showed differences in electrophysiological properties between SNI and sham operated mice. SNI ChIs showed a more hyperpolarized resting membrane potential together with a decreased input resistance in the NAc shell, suggesting decreased excitability of these interneurons. On the contrary, NAc shell PV-GaIs of SNI mice exhibited increased input resistance and fewer action potentials in response to depolarizing current injections, suggesting altered neuron function. SOM-GaIs of SNI mice showed opposing alterations in excitability, with NAc shell neurons requiring more current to induce action potential firing, whereas NAc core neurons required less current.Our findings indicate that NAc interneurons undergo electrophysiological changes in the early phase of pain chronification, exhibiting subregion-specific alterations. Since these interneurons have a significant impact on output signals from the NAc, this implies that they may play an important role in the development of mental comorbidities associated with neuropathic pain.