ArticleThe journal of headache and pain2025
The DRN-VLO pathway via distinct 5-HT synaptic mechanisms modulates neuropathic pain-induced depressive-like behaviors in mice.
Article in The journal of headache and pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- A glutamatergic ventrolateral periaqueductal gray-lateral habenula pathway is associated with depression-like behavioral measures in young adult male mice with trigeminal neuropathic pain.The journal of headache and pain · 2026Article
- Ventrolateral orbital cortex as a functional hub in chronic pain and comorbid depression.Frontiers in neuroscience · 2026Article
- Recent progress in chronic pain-related negative emotions and cognitive dysfunction: insights into the mechanisms underlying neural circuitry.Frontiers in cellular neuroscience · 2026Review
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13 authors.
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Abstract
backgroundThe neuronal activities within the dorsal raphe nucleus (DRN) and the ventrolateral orbital cortex (VLO) are strongly implicated in the development of depression, a condition comorbid with chronic pain. The goal of the present study was to determine whether and how the DRN-VLO pathway mediates chronic pain-induced depression.
methodsTrigeminal neuralgia was induced unilaterally by chronic constriction injury of the infraorbital nerve. Depressive-like behaviors were assessed by the open field test, forced swimming test and tail suspension test. Neuronal projection tracing, chemogenetic manipulations and pharmacological interventions were performed to determine the DRN-VLO pathway projection activity and pathway-mediated anti-depressant mechanism in mice with trigeminal neuralgia. The neuronal activity was assessed by measuring the c-Fos level using immunofluorescence imaging.
resultsThe VLO receives direct projection of the serotonergic neurons from the DRN. Anterograde or retrograde activation of the DRN-VLO pathway consistently produced anti-depressant effects in mice with neuropathic pain, whereas sustained inhibition of this pathway in healthy mice induced depressive-like behaviors. Activation of the 5-HT1A or 5-HT2A receptor in the VLO produced anti-depressant effects. Activation of the GABA
conclusionsThe present study has revealed that activation of the DRN-VLO pathway exerts an anti-depressant effect in mice with neuropathic pain, through stimulating the 5-HT2A receptors in the excitatory neurons and also the 5-HT1A receptors in the GABAergic interneurons via a dis-inhibition mechanism, to enhance neuronal activity of the VLO.
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