Distinct nucleus accumbens neural pathways underlie separate behavioral features of chronic pain and comorbid depression.

ABSTRACT: The comorbidity of depressive symptoms in chronic pain has been recognized as a key health issue. However, whether discrete circuits underlie behavioral subsets of chronic pain and comorbid depression has not been addressed. Here, we report that dopamine 2 (D2) receptor-expressing medium spiny neurons in the nucleus accumbens medial shell (mNAcSh) mediate pain hypersensitivity and depression-like behaviors in mice after nerve injury. Two separate neural pathways mediate different symptoms. The glutamatergic inputs from the anteromedial thalamic nucleus to mNAcSh D2 neurons that innervated orexin-expressing neurons in the lateral hypothalamic area contributed to pain regulation. In contrast, the lateral septum GABAergic inputs to mNAcSh D2 neurons that disinhibit the ventral pallidum glutam

SUBMITTER: Liu D 

PROVIDER: S-EPMC12321395 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature