A glutamatergic DRN-VTA pathway modulates neuropathic pain and comorbid anhedonia-like behavior in mice.

ABSTRACT: Chronic pain causes both physical suffering and comorbid mental symptoms such as anhedonia. However, the neural circuits and molecular mechanisms underlying these maladaptive behaviors remain elusive. Here using a mouse model, we report a pathway from vesicular glutamate transporter 3 neurons in the dorsal raphe nucleus to dopamine neurons in the ventral tegmental area (VGluT3^DRN→DA^VTA) wherein population-level activity in response to innocuous mechanical stimuli and sucrose consumption is inhibited by chronic neuropathic pain. Mechanistically, neuropathic pain dampens VGluT3^DRN → DA^VTA glutamatergic transmission and DA^VTA neural excitability. VGluT3^DRN → DA^VTA activation alleviates neuropathic pain and comorbid a

SUBMITTER: Wang XY 

PROVIDER: S-EPMC10447530 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature