ArticleProceedings of the National Academy of Sciences of the United States of America2024
Differential modulation of pain and associated anxiety by GABAergic neuronal circuits in the lateral habenula.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Distinct parafascicular neuronal ensembles mediate the sensory and affective dimensions of trigeminal neuralgia.The Journal of clinical investigation · 2026Article
- Dual regulatory mechanisms of the ZI-LHb circuit in SPS&S model mice: dissociable control of aversion and anxiety through distinct downstream targets.Molecular psychiatry · 2026Article
- MicroRNA-148a regulates depressive-like behaviors in mice via the Otx2/Dopaminergic signaling axis.Molecular psychiatry · 2026Article
- Opioid withdrawal engages a habenular subpopulation responsive to aversive states.bioRxiv : the preprint server for biology · 2026Article
- The lateral habenula as a master regulator of innate and learned social behaviors.Psychopharmacology · 2026Review
- Tuina Attenuates Pain with Reduced Serum Pain- and Inflammation-Related Mediators and p38 MAPK Phosphorylation in Selected Brain Regions in Rats with Knee Osteoarthritis.Journal of pain research · 2026Article
- Activation of the C3 Complement Pathway in the Hippocampus Produces Anxiodepressive Effects in a Mouse Model of Inflammation Pain.Molecular neurobiology · 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
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Authors and funding
15 authors.
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Abstract
Persistent pain frequently precipitates the development of anxiety disorders, yet the underlying mechanisms are not fully understood. In this study, we employed a mouse model that simulates trigeminal neuralgia and observed a marked reduction in the activity of GABAergic neurons in the lateral habenula (LHb), a critical region for modulating pain and anxiety. We utilized precise optogenetic and chemogenetic techniques to modulate these neurons, which significantly alleviated behaviors associated with pain and anxiety. Our investigations revealed an inhibitory pathway from the LHb GABAergic neurons to the posterior paraventricular thalamus. Activation of this pathway primarily mitigated pain-related behaviors, with minimal effects on anxiety. Conversely, interactions between GABAergic and glutamatergic neurons within the LHb were essential in alleviating both pain and anxiety following trigeminal nerve damage. Additionally, we identified that β-sitosterol interacts directly with LHb GABAergic neurons via the estrogen receptor α, providing dual therapeutic effects for both pain and anxiety. These findings highlight the critical role of reduced GABAergic neuronal activity in the LHb in the intersection of pain and anxiety, pointing to promising therapeutic possibilities.
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