Evidence map›Paper›PMID 40749060›Full record

ArticleScience advances2025

Neuronal Reg3β/macrophage TNF-α-mediated positive feedback signaling contributes to pain chronicity in a rat model of CRPS-I.

Huimin Nie, Boyu Liu, Chengyu Yin, Zishan Dong, Yushuang Pan, Peiyi Li, Qimiao Hu, Jie Wang, Yan Tai, Xiaomei Shao and 4 more

Abstract read
PubMed Full text at PMC Publisher
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Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Huimin NieDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.ORCID 0000-0002-6327-5613
Boyu LiuDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.ORCID 0000-0002-8801-8760
Chengyu YinDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.ORCID 0000-0001-5655-6292
Zishan DongDepartment of Pathophysiology, Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Hebei Medical University, Shijiazhuang, China.ORCID 0009-0009-5635-4768
Yushuang PanDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.ORCID 0000-0002-6138-2474
Peiyi LiDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
Qimiao HuDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
Jie WangDepartment of Rehabilitation in Traditional Chinese Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.ORCID 0000-0003-3267-8556
Yan TaiAcademy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Xiaomei ShaoDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
Guihua TianBeijing Friendship Hospital, Capital Medical University, Beijing, China.
Chuan WangDepartment of Pharmacology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, China.ORCID 0000-0003-3144-7094
Jianqiao FangDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
Boyi LiuDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.ORCID 0000-0001-9870-4548

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Complex regional pain syndrome type I (CRPS-I) develops after an initial injury. It causes prolonged pain that persists beyond the usual expected time for tissue healing. Mechanisms underlying pain chronicity of CRPS-I remain unknown. Here, we identified the presence of long-lasting infiltration of macrophages in local dorsal root ganglia (DRG) of a rat model of CRPS-I. We demonstrate that regenerating islet-derived 3β (Reg3β) is specifically produced by DRG neurons upon model establishment and functions as an important signaling molecule to drive proinflammatory macrophage infiltration in local DRG. Infiltrated macrophages produce TNF-α, which causes hyperexcitability of nociceptive DRG neurons and reciprocally promotes Reg3β overexpression and secretion from DRG neurons to recruit more macrophages. Our work reveals a positive feedback signaling conveyed by neuronal Reg3β/macrophage TNF-α that contributes to neuroinflammation in DRG, resulting in persistent pain in a rat model of CRPS-I. This finding provides insights into the neuroimmune interaction in local DRG that contributes to pain chronicity of CRPS-I.

Indexed as

Chronic PainMacrophagesNeuronsPancreatitis-Associated ProteinsReflex Sympathetic DystrophySignal TransductionTumor Necrosis Factor-alphaAnimalsDisease Models, AnimalGanglia, SpinalMaleRatsRats, Sprague-DawleyPancreatitis-Associated ProteinsTumor Necrosis Factor-alpha

Identifiers

PMID40749060
PMCPMC12315989

What OpenQuestion holds

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Registered trials

None linked

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.