Evidence map›Paper›PMID 25640077›Full record

ArticleNeuron2015

Tmem100 Is a Regulator of TRPA1-TRPV1 Complex and Contributes to Persistent Pain.

Hao-Jui Weng, Kush N Patel, Nathaniel A Jeske, Sonya M Bierbower, Wangyuan Zou, Vinod Tiwari, Qin Zheng, Zongxiang Tang, Gary C H Mo, Yan Wang and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed, 2 pooled it
9.9field-weighted citation impact, top 1% of its field
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

118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 180 citations in OpenAlex.

  1. Pooled it
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  14. Cytokines reprogram airway sensory neurons in asthma.bioRxiv : the preprint server for biology · 2024
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58 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 7 institutions in 3 countries.

Hao-Jui WengDepartments of Neuroscience and Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Dermatology, National Taiwan University Hospital, Taipei City 100, Taiwan.
Kush N PatelDepartments of Neuroscience and Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Nathaniel A JeskeDepartment of Physiology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Sonya M BierbowerDepartment of Physiology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Wangyuan ZouDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Vinod TiwariDepartment of Anesthesiology and Critical Care, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Qin ZhengDepartments of Neuroscience and Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Zongxiang TangNanjing University of Chinese Medicine, Nanjing 210046, China.
Gary C H MoDepartment of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Yan WangDepartments of Neuroscience and Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; West China School of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
Yixun GengDepartments of Neuroscience and Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Jin ZhangDepartments of Neuroscience and Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Yun GuanDepartment of Anesthesiology and Critical Care, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Armen N AkopianDepartment of Endodontics, University of Texas Health Science Center, San Antonio, TX 78229, USA. Electronic address: akopian@uthscsa.edu.
Xinzhong DongDepartments of Neuroscience and Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: xdong2@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · USThe University of Texas Health Science Center at San Antonio · USCentral South University · CNHoward Hughes Medical Institute · USNanjing University of Chinese Medicine · CNSichuan University · CN

Funding

Murine Mutagenesis CoreP30NS050274 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOLODKIN, ALEX L · 2005 to 2020
$10.9M
PATHOBIOLOGY OF OCCLUSIVE VASCULAR DISEASET32HL007446 · NHLBI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Jean Chrisostome Bopassa · 1985 to 2026
$8.9M
Neuronal subtype-specific plasticity in the acute to chronic pain transitionR01DE022750 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI CATERINA, MICHAEL J, DONG, XINZHONG · 2012 to 2016
$3.5M
Mrgs as New Target for the Treatment of Neuropathic PainR01NS070814 · NINDS · JOHNS HOPKINS UNIVERSITY · PI GUAN, YUN · 2011 to 2020
$3.2M
Scaffolding the Transition to Chronic PainR01NS082746 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI JESKE, NATHANIEL AARON · 2013 to 2017
$1.7M
Functional Analysis of Pirt and Pirt2: novel regulators of TRP channelsR01GM087369 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI DONG, XINZHONG · 2010 to 2013
$1.3M
Prolactin regulation of postoperative pain in males and femalesR01GM112747 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI AKOPIAN, ARMEN N · 2015 to 2018
$1.2M
INTERACTIONS OF TRPV1 AND TRPA1 AND INFLAMMATORY PAINR01DE019311 · NIDCR · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI AKOPIAN, ARMEN N · 2009 to 2010
$594k
M-Type K+ Channels: In Vivo Neuroprotective Role during Cerebrovascular StroF32NS079148 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BIERBOWER, SONYA MARIE · 2012 to 2014
$171k
Howard Hughes Medical InstituteNHLBI NIH HHS T32 HL007446NIDCR NIH HHS R01 DE019311NIDCR NIH HHS R01DE019311NIDCR NIH HHS R01 DE022750NIDCR NIH HHS R01DE022750NIGMS NIH HHS R01 GM087369NIGMS NIH HHS R01GM087369NIGMS NIH HHS R01 GM112747NINDS NIH HHS F32 NS079148NINDS NIH HHS F32NS079148NINDS NIH HHS P30 NS050274NINDS NIH HHS R01 NS070814NINDS NIH HHS R01 NS082746NINDS NIH HHS R01NS082746
6 · The paper itself

Abstract

TRPA1 and TRPV1 are crucial pain mediators, but how their interaction contributes to persistent pain is unknown. Here, we identify Tmem100 as a potentiating modulator of TRPA1-V1 complexes. Tmem100 is coexpressed and forms a complex with TRPA1 and TRPV1 in DRG neurons. Tmem100-deficient mice show a reduction in inflammatory mechanical hyperalgesia and TRPA1- but not TRPV1-mediated pain. Single-channel recording in a heterologous system reveals that Tmem100 selectively potentiates TRPA1 activity in a TRPV1-dependent manner. Mechanistically, Tmem100 weakens the association of TRPA1 and TRPV1, thereby releasing the inhibition of TRPA1 by TRPV1. A Tmem100 mutant, Tmem100-3Q, exerts the opposite effect; i.e., it enhances the association of TRPA1 and TRPV1 and strongly inhibits TRPA1. Strikingly, a cell-permeable peptide (CPP) containing the C-terminal sequence of Tmem100-3Q mimics its effect and inhibits persistent pain. Our study unveils a context-dependent modulation of the TRPA1-V1 complex, and Tmem100-3Q CPP is a promising pain therapy.

Indexed as

Action PotentialsAnimalsBiophysical PhenomenaCapsaicinCells, CulturedCHO CellsCricetulusDisease Models, AnimalElectric StimulationGanglia, SpinalHEK293 CellsHumansHyperalgesiaMaleMembrane ProteinsMiceCapsaicinMembrane ProteinsTmem100 protein, mouseTransient Receptor Potential ChannelsTRPA1 Cation ChannelTrpa1 protein, mouseTRPV1 protein, mouseTRPV Cation Channels

Identifiers

PMID25640077
PMCPMC4336228
OpenAlexW2029608563

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.