| First Author | Wang XY | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 5124 |
| PubMed ID | 37612268 | Mgi Jnum | J:355693 |
| Mgi Id | MGI:7521349 | Doi | 10.1038/s41467-023-40860-3 |
| Citation | Wang XY, et al. (2023) A glutamatergic DRN-VTA pathway modulates neuropathic pain and comorbid anhedonia-like behavior in mice. Nat Commun 14(1):5124 |
| abstractText | 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 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(DRN) --> DA(VTA) inhibition produces pain-like reflexive hypersensitivity and anhedonia-like behavior in intact mice. These findings reveal a crucial role for VGluT3(DRN) --> DA(VTA) --> D2/D1(NAcMed) pathway in establishing and modulating chronic pain and CAB. |
