ArticleProceedings of the National Academy of Sciences of the United States of America2020
Reversal of hyperactive subthalamic circuits differentially mitigates pain hypersensitivity phenotypes in parkinsonian mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Deep Brain Stimulation of the Subthalamic Nucleus Modulates Reward-Related Behavior: A Systematic Review.Frontiers in human neuroscience · 2020Pooled it
- NabioRxiv : the preprint server for biology · 2026Article
- The subthalamic nucleus-ventral pallidum projection targeting cholinergic circuits modulates chronic pain.PLoS biology · 2026Article
- Nigra-Subthalamic Dopaminergic Circuitry Modulates and Represents Distinct Pain Modality in Physiological and Pain States in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Subthalamic CaMKIIα-expressing neurons facilitate recovery from propofol anesthesia via the STN-ventral pallidum pathway.Cell biology and toxicology · 2026Article
- Targeting the oxidative stress-neuroinflammation axis: the mechanism of arctigenin's broad-spectrum analgesia with limited side effects.Frontiers in immunology · 2026Article
- Activation of the zona incerta GABAergic circuit for the treatment of pain hypersensitivity in Parkinson's disease mice model.The journal of headache and pain · 2025Article
- Dysfunction of subthalamic dopaminergic circuitry contributes to anxiety- and depression-like behaviors in 6-OHDA lesion-induced hemiparkinsonian mice.Acta pharmacologica Sinica · 2025Article
- A ventral pallidum-locus coeruleus-lateral hypothalamus pathway modulates brain arousal in freely behaving and isoflurane-anesthetized male mice.Nature communications · 2025Article
- The cardioprotective effects of acteoside in myocardial ischemia reperfusion injury and the underlying mechanism.BMC cardiovascular disorders · 2025Article
- Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Application of Optogenetics in Neurodegenerative Diseases.Cellular and molecular neurobiology · 2024Review
- Activation and polarization of striatal microglia and astrocytes are involved in bradykinesia and allodynia in early-stage parkinsonian mice.Fundamental research · 2024Article
- α4 nicotinic receptors on GABAergic neurons mediate a cholinergic analgesic circuit in the substantia nigra pars reticulata.Acta pharmacologica Sinica · 2024Article
- Activation of Pedunculopontine Tegmental Nucleus Alleviates the Pain Induced by the Lesion of Midbrain Dopaminergic Neurons.International journal of molecular sciences · 2024Article
- MOTS-c is an effective target for treating cancer-induced bone pain through the induction of AMPK-mediated mitochondrial biogenesis.Acta biochimica et biophysica Sinica · 2024Article
- Neurocircuitry basis of motor cortex-related analgesia as an emerging approach for chronic pain management.Nature. Mental health · 2024Article
- Insula→Amygdala and Insula→Thalamus Pathways Are Involved in Comorbid Chronic Pain and Depression-Like Behavior in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- The anterior cingulate cortex controls the hyperactivity in subthalamic neurons in male mice with comorbid chronic pain and depression.PLoS biology · 2024Article
- Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson's disease.Translational neurodegeneration · 2023Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although pain is a prevalent nonmotor symptom in Parkinson's disease (PD), it is undertreated, in part because of our limited understanding of the underlying mechanisms. Considering that the basal ganglia are implicated in pain sensation, and that their synaptic outputs are controlled by the subthalamic nucleus (STN), we hypothesized that the STN might play a critical role in parkinsonian pain hypersensitivity. To test this hypothesis, we established a unilateral parkinsonian mouse model with moderate lesions of dopaminergic neurons in the substantia nigra. The mice displayed pain hypersensitivity and neuronal hyperactivity in the ipsilesional STN and in central pain-processing nuclei. Optogenetic inhibition of STN neurons reversed pain hypersensitivity phenotypes in parkinsonian mice, while hyperactivity in the STN was sufficient to induce pain hypersensitivity in control mice. We further demonstrated that the STN differentially regulates thermal and mechanical pain thresholds through its projections to the substantia nigra pars reticulata (SNr) and the internal segment of the globus pallidus (GPi)/ventral pallidum (VP), respectively. Interestingly, optogenetic inhibition of STN-GPi/STN-VP and STN-SNr projections differentially elevated mechanical and thermal pain thresholds in parkinsonian mice. In summary, our results support the hypothesis that the STN and its divergent projections play critical roles in modulating pain processing under both physiological and parkinsonian conditions, and suggest that inhibition of individual STN projections may be a therapeutic strategy to relieve distinct pain phenotypes in PD.
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