Evidence map›Paper›PMID 27231153›Full record

ArticleGenes, brain, and behavior2016

Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test.

E E Young, C D Bryant, S E Lee, X Peng, B Cook, H K Nair, K J Dreher, X Zhang, A A Palmer, J M Chung and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Genes, brain, and behavior, 2016. 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
1.3field-weighted citation impact, top 22% 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, 15 citations in OpenAlex.

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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

13 authors at 6 institutions in 2 countries.

E E YoungDepartment of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
C D BryantDepartment of Pharmacology and Experimental Therapeutics and Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
S E LeeDepartment of Neuroscience & Cell Biology, University of Texas Medical Branch, Galveston, TX, USA.
X PengDepartment of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
B CookDepartment of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
H K NairDepartment of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
K J DreherDepartment of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
X ZhangDepartment of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
A A PalmerDepartment of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
J M ChungDepartment of Neuroscience & Cell Biology, University of Texas Medical Branch, Galveston, TX, USA.
J S MogilDepartment of Psychology and Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
E J CheslerMammalian Genetics & Genomics, Oak Ridge National Laboratory, Oak Ridge, TN, USA.
W R LariviereDepartment of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
University of Pittsburgh · USThe University of Texas Medical Branch at Galveston · USBoston University · USJackson Laboratory · USMcGill University · CAUniversity of Chicago · US

Funding

VISCERAL PAINP01NS011255 · NINDS · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI KAPHALIA, BHUPENDRA S · 1985 to 2012
$13.6M
Discovery of Addiction-Related Genes with Advanced Mouse ResourcesR01DA037927 · NIDA · JACKSON LABORATORY · PI CHESLER, ELISSA J · 2015 to 2025
$8.1M
NEUROPSYCHOPHARMACOLOLGY TRG FOR DRUG ABUSE RESEARCHT32DA007255 · NIDA · UNIVERSITY OF CHICAGO · PI VEZINA, PAUL R · 1991 to 2012
$5.9M
Mechanisms of Neuropathic PainR01NS031680 · NINDS · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI CHUNG, JIN M · 1994 to 2016
$4.1M
Systems Genetic Analysis of Methamphetamine's Motivational Effects in a Mouse AILR01DA021336 · NIDA · UNIVERSITY OF CHICAGO · PI PALMER, ABRAHAM A · 2006 to 2015
$4.0M
Data Structures, Algorithms and Tools for Ontological DiscoveryR01AA018776 · NIAAA · JACKSON LABORATORY · PI CHESLER, ELISSA J · 2010 to 2019
$3.9M
Gene to Phenotype Networks for Alcohol & Drug AddictionR01DA020677 · NIDA · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI GOLDOWITZ, DANIEL · 2006 to 2008
$2.2M
GENETICS OF NEUROPATHIC & INFLAMMATORY HYPERSENSITIVITYR01DA021198 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LARIVIERE, WILLIAM ROGER · 2007 to 2011
$1.7M
QTL Mapping of Multiple Analgesic ModalitiesR01DA015191 · NIDA · MCGILL UNIVERSITY · PI MOGIL, JEFFREY S · 2001 to 2005
$1.1M
Translational Genetics and Dopamine Signaling in Sensitivity to AmphetaminesF32DA026697 · NIDA · UNIVERSITY OF CHICAGO · PI BRYANT, CAMRON D · 2009 to 2009
$50k
NIAAA NIH HHS R01 AA018776NIDA NIH HHS F32 DA026697NIDA NIH HHS R01 DA015191NIDA NIH HHS R01 DA020677NIDA NIH HHS R01 DA021198NIDA NIH HHS R01 DA021336NIDA NIH HHS R01 DA037927NIDA NIH HHS T32 DA007255NINDS NIH HHS P01 NS011255NINDS NIH HHS R01 NS031680
6 · The paper itself

Abstract

Mechanical sensitivity is commonly affected in chronic pain and other neurological disorders. To discover mechanisms of individual differences in punctate mechanosensation, we performed quantitative trait locus (QTL) mapping of the response to von Frey monofilament stimulation in BXD recombinant inbred (BXD) mice. Significant loci were detected on mouse chromosome (Chr) 5 and 15, indicating the location of underlying polymorphisms that cause heritable variation in von Frey response. Convergent evidence from public gene expression data implicates candidate genes within the loci: von Frey thresholds were strongly correlated with baseline expression of Cacna2d1, Ift27 and Csnk1e in multiple brain regions of BXD strains. Systemic gabapentin and PF-670462, which target the protein products of Cacna2d1 and Csnk1e, respectively, significantly increased von Frey thresholds in a genotype-dependent manner in progenitors and BXD strains. Real-time polymerase chain reaction confirmed differential expression of Cacna2d1 and Csnk1e in multiple brain regions in progenitors and showed differential expression of Cacna2d1 and Csnk1e in the dorsal root ganglia of the progenitors and BXD strains grouped by QTL genotype. Thus, linkage mapping, transcript covariance and pharmacological testing suggest that genetic variation affecting Cacna2d1 and Csnk1e may contribute to individual differences in von Frey filament response. This study implicates Cacna2d1 and Ift27 in basal mechanosensation in line with their previously suspected role in mechanical hypersensitivity. Csnk1e is implicated for von Frey response for the first time. Further investigation is warranted to identify the specific polymorphisms involved and assess the relevance of these findings to clinical conditions of disturbed mechanosensation.

Indexed as

AminesAnalgesicsAnimalsCalcium ChannelsCasein Kinase ICyclohexanecarboxylic AcidsGabapentingamma-Aminobutyric AcidGanglia, SpinalMaleMechanotransduction, CellularMicePyrimidinesQuantitative Trait Locirab GTP-Binding ProteinsSensory ThresholdsAminesAnalgesicsCACNA2D1 protein, mouseCalcium ChannelsCasein Kinase ICyclohexanecarboxylic AcidsGabapentingamma-Aminobutyric Acidintraflagellar transport 27 protein, mousePF-670462Pyrimidinesrab GTP-Binding ProteinsCasein kinase 1linkage mappingmicroarrayquantitative trait locustranscript abundancevoltage-gated calcium channelsvon Frey

Identifiers

PMID27231153
PMCPMC4955286
OpenAlexW2407316653

What OpenQuestion holds

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Read underepoch 390

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 OpenQuestion graph.