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A glutamatergic DRN-VTA pathway modulates neuropathic pain and comorbid anhedonia-like behavior in mice.
- Source :
-
Nature communications [Nat Commun] 2023 Aug 23; Vol. 14 (1), pp. 5124. Date of Electronic Publication: 2023 Aug 23. - Publication Year :
- 2023
-
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 <superscript>DRN</superscript> →DA <superscript>VTA</superscript> ) wherein population-level activity in response to innocuous mechanical stimuli and sucrose consumption is inhibited by chronic neuropathic pain. Mechanistically, neuropathic pain dampens VGluT3 <superscript>DRN</superscript> → DA <superscript>VTA</superscript> glutamatergic transmission and DA <superscript>VTA</superscript> neural excitability. VGluT3 <superscript>DRN</superscript> → DA <superscript>VTA</superscript> 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 <superscript>DRN</superscript> → DA <superscript>VTA</superscript> inhibition produces pain-like reflexive hypersensitivity and anhedonia-like behavior in intact mice. These findings reveal a crucial role for VGluT3 <superscript>DRN</superscript> → DA <superscript>VTA</superscript> → D2/D1 <superscript>NAcMed</superscript> pathway in establishing and modulating chronic pain and CAB.<br /> (© 2023. Springer Nature Limited.)
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 37612268
- Full Text :
- https://doi.org/10.1038/s41467-023-40860-3