Evidence map›Paper›PMID 41530758›Full record

ArticleBMC medicine2026

5-HT2C receptors in the glutamatergic neurons of dorsal raphe nucleus orchestrate the comorbidity of pain and anxiety in mice.

Qi Zhang, Li Xie, Changmao Zhu, Siqi Yang, Xinying Zhang, Jingyao Huang, Yuanyuan Wang, Yawei Ji, Zifeng Wu, Chaoli Huang and 5 more

Abstract read
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In one paragraph

Article in BMC medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Qi Zhang *Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Li Xie *Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Changmao Zhu *Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Siqi YangDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Xinying ZhangDepartment of Anesthesiology, The People's Hospital of Rugao, Rugao Hospital Affiliated to Nantong University, Rugao, 226500, China.
Jingyao HuangDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Yuanyuan WangDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Yawei JiDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Zifeng WuDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Chaoli HuangDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Di WangDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Ling YangDepartment of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
Chun YangDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. chunyang@njmu.edu.cn.
Suwan HuDepartment of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. swhu@njmu.edu.cn.
Riyue JiangDepartment of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. riyuejiang@jsph.org.cn.

Funding

National Natural Science Foundation of China 82571395
6 · The paper itself

Abstract

backgroundPain-anxiety comorbidity represents a prevalent clinical concern. This study aims to investigate the molecular mechanisms underlying the comorbidities via focusing on the activity of dorsal raphe nucleus (DRN) glutamatergic neurons and the functional role of their 5-hydroxytryptamine 2C (5-HT2C) receptors in relation to gut microbiota.

methodsWe established a Complete Freund's Adjuvant (CFA)-induced pain-anxiety comorbidity model in mice and systematically investigated the role of the brain-gut axis in the comorbidity using behavioral phenotyping, molecular biology, pharmacological/chemogenetic modulation, and gut microbiota profiling.

resultsHeightened activity in the glutamatergic neurons of the DRN was found in mice with comorbidity. Chemogenetic activation of DRN glutamatergic neurons replicated the comorbid phenotype in naïve mice, while the selective inhibition of DRN glutamatergic neurons effectively reversed the behavioral and physiological impairments induced by CFA. Notably, a significant upregulation in the protein levels of 5-HT2C receptors in the DRN was detected in the comorbid state. Bidirectional manipulation of 5-HT2C receptors in the DRN glutamatergic neurons bidirectionally regulates neuronal excitability and comorbid phenotypes: agonism or overexpression exacerbates comorbidity, while antagonism or knockdown attenuates CFA-induced deficits.

conclusionsThese findings uncover the role of 5-HT2C receptors in DRN glutamatergic neurons in pain-anxiety comorbidity, thereby presenting novel targets for potential therapeutic interventions.

Indexed as

AnxietyDorsal Raphe NucleusNeuronsPainReceptor, Serotonin, 5-HT2CAnimalsComorbidityDisease Models, AnimalFreund's AdjuvantMaleMiceMice, Inbred C57BLFreund's AdjuvantReceptor, Serotonin, 5-HT2C5-HT2C receptorsAnxietyComorbidityDorsal raphe nucleusPain

Identifiers

PMID41530758
PMCPMC12888131

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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.