Evidence map›Paper›PMID 35705078›Full record

ArticleNeuron2022

Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms.

Teodora Trendafilova, Kaustubh Adhikari, Annina B Schmid, Ryan Patel, Erika Polgár, Kim I Chisholm, Steven J Middleton, Kieran Boyle, Allen C Dickie, Evangelia Semizoglou and 23 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

9 citing papers in PubMed, 17 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors at 13 institutions in 12 countries.

Teodora TrendafilovaNuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK.
Kaustubh AdhikariSchool of Mathematics and Statistics, Faculty of Science, Technology, Engineering and Mathematics, The Open University, Milton Keynes, UK; Department of Genetics, Evolution and Environment, University College London, London, UK; Department of Cell and Developmental Biology, University College London, London, UK.
Annina B SchmidNuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK.
Ryan PatelDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Erika PolgárSchool of Psychology and Neuroscience, University of Glasgow, Glasgow, UK.
Kim I ChisholmWolfson Centre for Age-Related Diseases, King's College London, London, UK.
Steven J MiddletonNuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK.
Kieran BoyleSchool of Psychology and Neuroscience, University of Glasgow, Glasgow, UK.
Allen C DickieSchool of Psychology and Neuroscience, University of Glasgow, Glasgow, UK.
Evangelia SemizoglouWolfson Centre for Age-Related Diseases, King's College London, London, UK.
Jimena Perez-SanchezNuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK.
Andrew M BellSchool of Psychology and Neuroscience, University of Glasgow, Glasgow, UK.
Luis Miguel Ramirez-AristeguietaQST Lab. Faculty of Odontology, Universidad de Antioquia, Medellin, Colombia.
Samar KhouryMcGill University and Genome Quebec Innovation Centre, Montreal, QC, Canada.
Aleksandar IvanovDepartment of Physiology Anatomy and Genetics, University of Oxford, Oxford, UK.
Hendrik WildnerInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Eleanor FerrisNuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK.
Juan-Camilo Chacón-DuqueDepartment of Genetics, Evolution and Environment, University College London, London, UK; Centre for Palaeogenetics, Stockholm, Sweden; Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden.
Sophie SokolowLaboratoire de Pharmacodynamie et de Thérapeutique Faculté de Médecine Université Libre de Bruxelles, Brussels, Belgium; School of Nursing, University of California, Los Angeles, Los Angeles, CA, USA.
Mohamed A Saad BoghdadyNuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK.
André HerchuelzLaboratoire de Pharmacodynamie et de Thérapeutique Faculté de Médecine Université Libre de Bruxelles, Brussels, Belgium.
Pierre FauxCNRS, EFS, ADES, Aix-Marseille Université, Marseille, France.
Giovanni PolettiUnidad de Neurobiologia Molecular y Genética, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
Carla GalloUnidad de Neurobiologia Molecular y Genética, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
Francisco RothhammerInstituto de Alta Investigación, Universidad de Tarapacá, Arica, Chile.
Gabriel BedoyaGENMOL (Genética Molecular), Universidad de Antioquia, Medellin, Colombia.
Hanns Ulrich ZeilhoferInstitute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.
Luda DiatchenkoMcGill University and Genome Quebec Innovation Centre, Montreal, QC, Canada.
Stephen B McMahonWolfson Centre for Age-Related Diseases, King's College London, London, UK.
Andrew J ToddSchool of Psychology and Neuroscience, University of Glasgow, Glasgow, UK.
Anthony H DickensonDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Andres Ruiz-LinaresDepartment of Genetics, Evolution and Environment, University College London, London, UK; CNRS, EFS, ADES, Aix-Marseille Université, Marseille, France; Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China. Electronic address: andresruiz@fudan.edu.cn.
David L BennettNuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK. Electronic address: david.bennett@ndcn.ox.ac.uk.
University of Oxford · GBUniversity of Glasgow · GBKing's College London · GBCentre National de la Recherche Scientifique · FRMcGill University and Génome Québec Innovation Centre · CAUniversidad de Antioquia · COUniversidad Peruana Cayetano Heredia · PEUniversité Libre de Bruxelles · BEUniversity College London · GBUniversity of Zurich · CHStockholm University · SEThe Open University · GBUniversity of Tarapacá · CL

Funding

Department of HealthMedical Research Council MR/T020113/1Medical Research Council MR/V033638/1Wellcome Trust 095698Z/11/ZWellcome Trust 102645/Z/13/ZWellcome Trust 202747/Z/16/ZWellcome Trust 222101Wellcome Trust 222101/Z/20/ZWellcome Trust WT107055AIAWellcome Trust WT219433/Z/19/Z
6 · The paper itself

Abstract

Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is "wind-up," in which dorsal horn spinal neurons increase their response to repeated nociceptor stimulation. To understand the genetic basis of temporal summation, we undertook a GWAS of wind-up in healthy human volunteers and found significant association with SLC8A3 encoding sodium-calcium exchanger type 3 (NCX3). NCX3 was expressed in mouse dorsal horn neurons, and mice lacking NCX3 showed normal, acute pain but hypersensitivity to the second phase of the formalin test and chronic constriction injury. Dorsal horn neurons lacking NCX3 showed increased intracellular calcium following repetitive stimulation, slowed calcium clearance, and increased wind-up. Moreover, virally mediated enhanced spinal expression of NCX3 reduced central sensitization. Our study highlights Ca

Indexed as

CalciumSodium-Calcium ExchangerAnimalsHumansMicePainPosterior Horn CellsPsychophysicsCalciumSLC38A3 protein, humanSlc8a3 protein, mouseSodium-Calcium Exchangercentral sensitizationGWASin vivo calcium imagingin vivo electrophysiologypainspinal cordtemporal summationwind-up

Identifiers

PMID35705078
PMCPMC7613464
OpenAlexW4282842399

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.