Evidence mapPaperPMID 41340091Full record

ArticleCellular & molecular biology letters2025

Trigeminal nerve root compression induced neuroinflammatory response promotes mechanical allodynia through the CGRP/SP-Piezo2 axis via Ca

Xinyue Liao, Zhaoke Luo, Feng Huang, Yiqian Wang, Zhangying Zeng, Weihang Liao, Yating Ou, Xuemei Wu, Feng Wang, Daoshu Luo

Abstract read
In one paragraph

Article in Cellular & molecular biology letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Xinyue Liao *Laboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, 350122, Fuzhou, China.ORCID http://orcid.org/0000-0001-5302-8793
Zhaoke Luo *Laboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, 350122, Fuzhou, China.ORCID http://orcid.org/0000-0001-8648-076X
Feng Huang *Laboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, 350122, Fuzhou, China.
Yiqian WangLaboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, 350122, Fuzhou, China.
Zhangying ZengLaboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, 350122, Fuzhou, China.
Weihang LiaoLaboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, 350122, Fuzhou, China.
Yating OuLaboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, 350122, Fuzhou, China.
Xuemei WuLaboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, 350122, Fuzhou, China.
Feng WangLaboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, 350122, Fuzhou, China. fjwf95168@163.com.
Daoshu LuoLaboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, 350122, Fuzhou, China. luods2004@fjmu.edu.cn.ORCID http://orcid.org/0000-0001-9013-1052

Funding

Joint Funds for the innovation of science and Technology,Fujian province 2023Y9005National Natural Science Foundation of China 82171213
6 · The paper itself

Abstract

Trigeminal neuralgia (TN) is one of the most severe types of neuropathic pain, but its pathological mechanisms remain unknown. In this study, we identified a unique neuroinflammatory response induced by chronic compression of trigeminal root entry zone (TREZ) in a TN rat model, establishing a connection between ATP-driven intracellular pathways and Piezo2-mediated mechanotransduction. Piezo2, the pain-related neuropeptide calcitonin gene-related peptide (CGRP) receptor complex CRLR-RAMP1 and the neuropeptide substance-P (SP) receptor NK1R are co-expressed on rat Merkel cells. Protein kinase C (PKC) plays a crucial role in upregulating Piezo2 and CGRP/SP expression in both the trigeminal ganglion (TG) and whisker pad, thereby facilitating orofacial mechanical allodynia in TN rats. Furthermore, the inhibition of cAMP signaling in the whisker pads effectively alleviated mechanical allodynia, while Piezo2 knockdown in both the TG and whisker pads significantly reversed db cAMP-induced allodynia. In vitro studies demonstrated that extracellular ATP not only enhances CGRP and SP expression but also induces Piezo2 expression through Ca2+-dependent activation of ERK1/2 and p38 MAPK cascades, mediated by specific transcription factors. These findings reveal that peripheral sensitization in TN is mediated through a Ca2+-CGRP/SP-Piezo2 positive feedback loop, dependent on the neuroinflammatory response along the TG neuron–Merkel cell axis as a prerequisite condition. This discovery provides a novel insight into the pathogenesis of TN.

Indexed as

Calcitonin Gene-Related PeptideCalcium SignalingHyperalgesiaIon ChannelsNeuroinflammatory DiseasesSubstance PTrigeminal NerveTrigeminal NeuralgiaAdenosine TriphosphateAnimalsMaleRatsRats, Sprague-DawleyTrigeminal GanglionAdenosine TriphosphateCalcitonin Gene-Related PeptideIon Channelspiezo2 protein, ratSubstance PCa2+-PKCCGRP/SPNeuroinflammationPiezo2Trigeminal neuralgia

Identifiers

PMID41340091
PMCPMC12801477

What Socratic holds

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Registered trials

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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 Socratic graph.