Evidence map›Paper›PMID 41204078›Full record

ArticleThe journal of headache and pain2025

Activation of the zona incerta GABAergic circuit for the treatment of pain hypersensitivity in Parkinson's disease mice model.

Juntao Cui, Junliang Qian, Yaying Shi, Yanhong Liu, Le Qu, Wenting Jia, Junxia Xie, Limin Shi

Abstract read
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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 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Juntao Cui *Department of Physiology, School of Basic Medicine, Institute of Brain Science and Disease, Shandong Key Laboratory of Pathogenesis and Prevention of Brain Diseases, Qingdao University, Qingdao, China.
Junliang Qian *Department of Physiology, School of Basic Medicine, Institute of Brain Science and Disease, Shandong Key Laboratory of Pathogenesis and Prevention of Brain Diseases, Qingdao University, Qingdao, China.
Yaying ShiDepartment of Physiology, School of Basic Medicine, Institute of Brain Science and Disease, Shandong Key Laboratory of Pathogenesis and Prevention of Brain Diseases, Qingdao University, Qingdao, China.
Yanhong LiuDepartment of Physiology, School of Basic Medicine, Institute of Brain Science and Disease, Shandong Key Laboratory of Pathogenesis and Prevention of Brain Diseases, Qingdao University, Qingdao, China.
Le QuDepartment of Physiology, School of Basic Medicine, Institute of Brain Science and Disease, Shandong Key Laboratory of Pathogenesis and Prevention of Brain Diseases, Qingdao University, Qingdao, China.
Wenting JiaDepartment of Physiology, School of Basic Medicine, Institute of Brain Science and Disease, Shandong Key Laboratory of Pathogenesis and Prevention of Brain Diseases, Qingdao University, Qingdao, China.
Junxia XieDepartment of Physiology, School of Basic Medicine, Institute of Brain Science and Disease, Shandong Key Laboratory of Pathogenesis and Prevention of Brain Diseases, Qingdao University, Qingdao, China. jxiaxie@public.qd.sd.cn.
Limin ShiDepartment of Physiology, School of Basic Medicine, Institute of Brain Science and Disease, Shandong Key Laboratory of Pathogenesis and Prevention of Brain Diseases, Qingdao University, Qingdao, China. liminshi@qdu.edu.cn.

Funding

National Natural Science Foundation of China 32171132National Natural Science Foundation of China 32471049Natural Science Foundation of Shandong Province ZR2021MC167
6 · The paper itself

Abstract

backgroundPain is a prevalent and frequently undertreated non-motor symptom in Parkinson's disease (PD), affecting approximately 40% to 85% of patients. The zona incerta (ZI) is primarily an inhibitory subthalamic region involved in nociceptive neurotransmission. Previous studies demonstrated that the ZI is an important gamma-aminobutyric acid-ergic (GABAergic) source to the ventral tegmental area (VTA), but whether the ZI-VTA pathway participates in PD pain processing is still unclear. Given that deep brain stimulation targeting the ZI has demonstrated beneficial effects on pain perception in PD patients, we hypothesized that GABAergic signaling within the ZI may play a critical role in PD pain hypersensitivity.

methodsMale C57BL/6 mice and Vgat-Cre mice were used in the experiments. A unilateral PD mouse model was established through the injection of 6-hydroxydopamine (6-OHDA) into the striatum. We performed von Frey test and hot/cold plate tests to assess nociceptive behavior in PD mice. We then employed fiber photometry, chemogenetic, and optogenetic approaches to investigate the roles of ZI GABAergic neurons and ZI

resultsActivation of ZI GABAergic neurons alleviated pain hypersensitivity in PD mouse model, whereas inhibition of these neurons was sufficient to induce pain hypersensitivity in control naïve mice. Furthermore, we demonstrated that projections from GABAergic neurons in the ZI to VTA are involved in regulating pain associated with PD. Chemogenetic and optogenetic activation of the ZI

conclusionsOur results indicate that the ZI GABAergic neurons and their downstream projections to the VTA play crucial roles in modulating pain processing under both physiological conditions and during PD states. This research offers fresh perspectives on the PD pain mechanism. Considering our previous report indicating that stimulation of ZI GABAergic neurons improved motor performance in 6-OHDA-lesioned mice, we propose that the ZI may serve a dual regulatory function concerning both motor behavior and pain response associated with PD.

Indexed as

GABAergic NeuronsHyperalgesiaParkinson DiseaseZona IncertaAnimalsDisease Models, AnimalMaleMiceMice, Inbred C57BLMice, TransgenicOxidopamineVentral Tegmental AreaOxidopamineGABAPain hypersensitivityParkinson’s diseaseVentral tegmental areaZona incerta

Identifiers

PMID41204078
PMCPMC12595850

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.