ArticleActa neuropathologica communications2020
Tacr3 in the lateral habenula differentially regulates orofacial allodynia and anxiety-like behaviors in a mouse model of trigeminal neuralgia.
Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Trigeminal neuralgia and genetics: A systematic review.Molecular painPooled it
- Distinct parafascicular neuronal ensembles mediate the sensory and affective dimensions of trigeminal neuralgia.The Journal of clinical investigation · 2026Article
- PRPF8-associated retinitis pigmentosa variant induces human neural retina-autonomous photoreceptor defects.Scientific reports · 2026Article
- Recent progress in chronic pain-related negative emotions and cognitive dysfunction: insights into the mechanisms underlying neural circuitry.Frontiers in cellular neuroscience · 2026Review
- Article
- Around-the-clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the PI3K/SGK1/Foxo3 signaling pathway.Journal of translational medicine · 2025Article
- Differential modulation of pain and associated anxiety by GABAergic neuronal circuits in the lateral habenula.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Noval insights and therapeutic strategies for tumor-induced kidney pathologies.Journal of experimental & clinical cancer research : CR · 2024Article
- Foxg1 Modulation of the Prkcd Gene in the Lateral Habenula Mediates Trigeminal Neuralgia-Associated Anxiety-Like Behaviors in Mice.Molecular neurobiology · 2024Article
- TET1 Participates in Complete Freund's Adjuvant-induced Trigeminal Inflammatory Pain by Regulating Kv7.2 in a Mouse Model.Neuroscience bulletin · 2024Article
- Interplay between hippocampal TACR3 and systemic testosterone in regulating anxiety-associated synaptic plasticity.Molecular psychiatry · 2024Article
- SRRM4-mediated REST to REST4 dysregulation promotes tumor growth and neural adaptation in breast cancer leading to brain metastasis.Neuro-oncology · 2024Article
- Article
- Role of Glutamatergic Projections from Lateral Habenula to Ventral Tegmental Area in Inflammatory Pain-Related Spatial Working Memory Deficits.Biomedicines · 2023Article
- Evaluation of anxiety disorder in patients with trigeminal neuralgia.Surgical neurology international · 2023Article
- Tachykinin receptor 3 in the lateral habenula alleviates pain and anxiety comorbidity in mice.Frontiers in immunology · 2023Article
- Brain nuclei and neural circuits in neuropathic pain and brain modulation mechanisms of acupuncture: a review on animal-based experimental research.Frontiers in neuroscience · 2023Review
- Glimepiride mitigates tauopathy and neuroinflammation in P301S transgenic mice: role of AKT/GSK3β signaling.Inflammopharmacology · 2022Article
- HMGB1 in the mPFC governs comorbid anxiety in neuropathic pain.The journal of headache and pain · 2022Article
- Article
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9 authors at 2 institutions in 1 country.
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Abstract
Trigeminal neuralgia (TN) is debilitating and is usually accompanied by mood disorders. The lateral habenula (LHb) is considered to be involved in the modulation of pain and mood disorders, and the present study aimed to determine if and how the LHb participates in the development of pain and anxiety in TN. To address this issue, a mouse model of partial transection of the infraorbital nerve (pT-ION) was established. pT-ION induced stable and long-lasting primary and secondary orofacial allodynia and anxiety-like behaviors that correlated with the increased excitability of LHb neurons. Adeno-associated virus (AAV)-mediated expression of hM4D(Gi) in glutamatergic neurons of the unilateral LHb followed by clozapine-N-oxide application relieved pT-ION-induced anxiety-like behaviors but not allodynia. Immunofluorescence validated the successful infection of AAV in the LHb, and microarray analysis showed changes in gene expression in the LHb of mice showing allodynia and anxiety-like behaviors after pT-ION. Among these differentially expressed genes was Tacr3, the downregulation of which was validated by RT-qPCR. Rescuing the downregulation of Tacr3 by AAV-mediated Tacr3 overexpression in the unilateral LHb significantly reversed pT-ION-induced anxiety-like behaviors but not allodynia. Whole-cell patch clamp recording showed that Tacr3 overexpression suppressed nerve injury-induced hyperexcitation of LHb neurons, and western blotting showed that the pT-ION-induced upregulation of p-CaMKII was reversed by AAV-mediated Tacr3 overexpression or chemicogenetic inhibition of glutamatergic neurons in the LHb. Moreover, not only anxiety-like behaviors, but also allodynia after pT-ION were significantly alleviated by chemicogenetic inhibition of bilateral LHb neurons or by bilateral Tacr3 overexpression in the LHb. In conclusion, Tacr3 in the LHb plays a protective role in treating trigeminal nerve injury-induced allodynia and anxiety-like behaviors by suppressing the hyperexcitability of LHb neurons. These findings provide a rationale for suppressing unilateral or bilateral LHb activity by targeting Tacr3 in treating the anxiety and pain associated with TN.
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