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Papers of the Week

Papers: 19 Aug 2023 - 25 Aug 2023

Basic Science, Psychology

Animal Studies, Molecular/Cellular, Neurobiology

Neuropathic Pain, Psychological/Comorbidities

2023 Aug 23

Nat Commun




Editor's Pick

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


Wang XY, Jia WB, Xu X, Chen R, Wang LB, Su XJ, Xu PF, Liu XQ, Wen J, Song XY, Liu YY, Zhang Z, Liu XF, Zhang Y


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→DA) wherein population-level activity in response to innocuous mechanical stimuli and sucrose consumption is inhibited by chronic neuropathic pain. Mechanistically, neuropathic pain dampens VGluT3 → DA glutamatergic transmission and DA neural excitability. VGluT3 → DA activation alleviates neuropathic pain and comorbid anhedonia-like behavior (CAB) by releasing glutamate, which subsequently promotes DA release in the nucleus accumbens medial shell (NAcMed) and produces analgesic and anti-anhedonia effects via D2 and D1 receptors, respectively. In addition, VGluT3 → DA inhibition produces pain-like reflexive hypersensitivity and anhedonia-like behavior in intact mice. These findings reveal a crucial role for VGluT3 → DA → D2/D1 pathway in establishing and modulating chronic pain and CAB.