Evidence map›Paper›PMID 26754745›Full record

ArticleArthritis research & therapy2016

Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner.

Elizabeth S Fernandes, Fiona A Russell, Khadija M Alawi, Claire Sand, Lihuan Liang, Robin Salamon, Jennifer V Bodkin, Aisah A Aubdool, Matthew Arno, Clive Gentry and 5 more

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 7% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. [A preliminary analysis of the clinical characteristics of patients with temperature-sensitive temporomandibular joint disorder syndrome].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2025
    Article
  4. Histone Methyltransferase G9a in Primary Sensory Neurons Promotes Inflammatory Pain and Transcription ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
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  16. CBS-Induced HEvidence-based complementary and alternative medicine : eCAM · 2020
    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

15 authors at 1 institution in 2 countries.

Elizabeth S FernandesCentre for Cardiovascular Excellence, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. elizabeth.fernandes@kcl.ac.uk.
Fiona A RussellCentre for Cardiovascular Excellence, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. fiona.a.russell@kcl.ac.uk.
Khadija M AlawiCentre for Cardiovascular Excellence, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. khadija.k.alawi@kcl.ac.uk.
Claire SandCentre for Cardiovascular Excellence, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. claire.sand@hotmail.com.
Lihuan LiangCentre for Cardiovascular Excellence, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. liangli@medimmune.com.
Robin SalamonCentre for Cardiovascular Excellence, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. rsalamon@ulb.ac.be.
Jennifer V BodkinCentre for Cardiovascular Excellence, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. jenniferbodkin@hotmail.co.uk.
Aisah A AubdoolCentre for Cardiovascular Excellence, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. aisah.aubdool@kcl.ac.uk.
Matthew ArnoGenomics Centre, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. matthew.arno@kcl.ac.uk.
Clive GentryWolfson Centre for Age-Related Diseases, Guy's Campus, King's College London, London, SE1 1UL, UK. clive.gentry@kcl.ac.uk.
Sarah-Jane SmillieCentre for Cardiovascular Excellence, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. smilliesj@hotmail.com.
Stuart BevanWolfson Centre for Age-Related Diseases, Guy's Campus, King's College London, London, SE1 1UL, UK. stuart.bevan@kcl.ac.uk.
Julie E KeebleInstitute of Pharmaceutical Science, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. julie.keeble@kcl.ac.uk.
Marzia MalcangioWolfson Centre for Age-Related Diseases, Guy's Campus, King's College London, London, SE1 1UL, UK. marzia.malcangio@kcl.ac.uk.
Susan D BrainCentre for Cardiovascular Excellence, Waterloo Campus, King's College London, Franklin-Wilkins Building, 150 Stamford St, London, SE1 9NH, UK. sue.brain@kcl.ac.uk.
King's College London · GB

Funding

Versus Arthritis 19296Versus Arthritis 20264
6 · The paper itself

Abstract

backgroundThe effect of cold temperature on arthritis symptoms is unclear. The aim of this study was to investigate how environmental cold affects pain and blood flow in mono-arthritic mice, and examine a role for transient receptor potential ankyrin 1 (TRPA1), a ligand-gated cation channel that can act as a cold sensor.

methodsMono-arthritis was induced by unilateral intra-articular injection of complete Freund's adjuvant (CFA) in CD1 mice, and in mice either lacking TRPA1 (TRPA1 KO) or respective wildtypes (WT). Two weeks later, nociception and joint blood flow were measured following exposure to 10 °C (1 h) or room temperature (RT). Primary mechanical hyperalgesia in the knee was measured by pressure application apparatus; secondary mechanical hyperalgesia by automated von Frey system; thermal hyperalgesia by Hargreaves technique, and weight bearing by the incapacitance test. Joint blood flow was recorded by full-field laser perfusion imager (FLPI) and using clearance of (99m)Technetium. Blood flow was assessed after pretreatment with antagonists of either TRPA1 (HC-030031), substance P neurokinin 1 (NK1) receptors (SR140333) or calcitonin gene-related peptide (CGRP) (CGRP8-37). TRPA1, TAC-1 and CGRP mRNA levels were examined in dorsal root ganglia, synovial membrane and patellar cartilage samples.

resultsCold exposure caused bilateral primary mechanical hyperalgesia 2 weeks after CFA injection, in a TRPA1-dependent manner. In animals maintained at RT, clearance techniques and FLPI showed that CFA-treated joints exhibited lower blood flow than saline-treated joints. In cold-exposed animals, this reduction in blood flow disappears, and increased blood flow in the CFA-treated joint is observed using FLPI. Cold-induced increased blood flow in CFA-treated joints was blocked by HC-030031 and not observed in TRPA1 KOs. Cold exposure increased TRPA1 mRNA levels in patellar cartilage, whilst reducing it in synovial membranes from CFA-treated joints.

conclusionsWe provide evidence that environmental cold exposure enhances pain and increases blood flow in a mono-arthritis model. These changes are dependent on TRPA1. Thus, TRPA1 may act locally within the joint to influence blood flow via sensory nerves, in addition to its established nociceptive actions.

Indexed as

AnimalsArthritis, ExperimentalBlood Flow VelocityCold TemperatureFreund's AdjuvantHindlimbInjections, Intra-ArticularJointsMaleMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutPain MeasurementPain ThresholdTransient Receptor Potential ChannelsFreund's AdjuvantTransient Receptor Potential ChannelsTRPA1 Cation ChannelTrpa1 protein, mouse

Identifiers

PMID26754745
PMCPMC4718045
OpenAlexW2237896552

What OpenQuestion 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 OpenQuestion graph.