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Activation of parabrachial nucleus - ventral tegmental area pathway underlies the comorbid depression in chronic neuropathic pain in mice

ABSTRACT: Summary Depression symptoms are often found in patients suffering from chronic pain, a phenomenon that is yet to be understood mechanistically. Here, we systematically investigate the cellular mechanisms and circuits underlying the chronic-pain-induced depression behavior. We show that the development of chronic pain is accompanied by depressive-like behaviors in a mouse model of trigeminal neuralgia. In parallel, we observe increased activity of the dopaminergic (DA) neuron in the midbrain ventral tegmental area (VTA), and inhibition of this elevated VTA DA neuron activity reverses the behavioral manifestations of depression. Further studies establish a pathway of glutamatergic projections from the spinal trigeminal subnucleus caudalis (Sp5C) to the lateral parabrachial nucleus (LPBN) and then to the VTA. These glutamatergic projections form a direct circuit that controls the development of the depression-like behavior under the state of the chronic neuropathic pain. Graphical abstract Highlights • Chronic neuropathic pain induces depression-like behaviors• Depression behaviors are related to increased activity of VTA DA neurons• Direct glutamatergic projections link Sp5C-LPBN-VTA• Activation of Sp5C-LPBN-VTA leads to increased DA neuron firing and depression Zhang et al. show that a chronic trigeminal neuralgia leads to depression, which is caused by increased activity of dopamine neurons in the midbrain. The neuronal circuits linking the spinal trigeminal subnucleus caudalis, the lateral parabrachial nucleus, and the ventral tegmental area underlie this increased activity of dopamine neurons.

SUBMITTER: Zhang L

PROVIDER: S-EPMC8578703 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Parabrachial nucleus circuit governs neuropathic pain-like behavior.

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