Evidence map›Paper›PMID 21843914›Full record

ArticlePain2011

Selective targeting of ASIC3 using artificial miRNAs inhibits primary and secondary hyperalgesia after muscle inflammation.

Roxanne Y Walder, Mamta Gautam, Steven P Wilson, Christopher J Benson, Kathleen A Sluka

Open access · greenAbstract read
In one paragraph

Article in Pain, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

46 citing papers in PubMed, 71 citations in OpenAlex.

  1. Review
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  9. Review
  10. Review
  11. Article
  12. Article
  13. Acid-sensing ion channels in sensory signaling.American journal of physiology. Renal physiology · 2020
    Review
  14. A dual role for peripheral GDNF signaling in nociception and cardiovascular reflexes in the mouse.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Drugging the pain epigenome.Nature reviews. Neurology · 2017
    Review
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

5 authors at 2 institutions in 1 country.

Roxanne Y WalderPhysical Therapy and Rehabilitation Sciences Graduate Program, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA Neuroscience Graduate Program, Pain Research Program, The University of Iowa, Iowa City, IA, USA Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, USA Department of Internal Medicine, Pain Research Program, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.
Mamta Gautam
Steven P Wilson
Christopher J Benson
Kathleen A Sluka
University of Iowa · USUniversity of South Carolina · US

Funding

Role of ASIC3 in the Etiology of FibromyalgiaR01AR053509 · NIAMS · UNIVERSITY OF IOWA · PI SLUKA, KATHLEEN A · 2006 to 2010
$3.2M
NIAMS NIH HHS R01 AR053509NIAMS NIH HHS R01AR053509NIAMS NIH HHS R01AR053509S1
6 · The paper itself

Abstract

Acid-sensing ion channels (ASICs) are activated by acidic pH and may play a significant role in the development of hyperalgesia. Earlier studies show ASIC3 is important for induction of hyperalgesia after muscle insult using ASIC3-/- mice. ASIC3-/- mice lack ASIC3 throughout the body, and the distribution and composition of ASICs could be different from wild-type mice. We therefore tested whether knockdown of ASIC3 in primary afferents innervating muscle of adult wild-type mice prevented development of hyperalgesia to muscle inflammation. We cloned and characterized artificial miRNAs (miR-ASIC3) directed against mouse ASIC3 (mASIC3) to downregulate ASIC3 expression in vitro and in vivo. In CHO-K1 cells transfected with mASIC3 cDNA in culture, the miR-ASIC3 constructs inhibited protein expression of mASIC3 and acidic pH-evoked currents and had no effect on protein expression or acidic pH-evoked currents of ASIC1a. When miR-ASIC3 was used in vivo, delivered into the muscle of mice using a herpes simplex viral vector, both muscle and paw mechanical hyperalgesia were reduced after carrageenan-induced muscle inflammation. ASIC3 mRNA in DRG and protein levels in muscle were decreased in vivo by miR-ASIC3. In CHO-K1 cells co-transfected with ASIC1a and ASIC3, miR-ASIC3 reduced the amplitude of acidic pH-evoked currents, suggesting an overall inhibition in the surface expression of heteromeric ASIC3-containing channels. Our results show, for the first time, that reducing ASIC3 in vivo in primary afferent fibers innervating muscle prevents the development of inflammatory hyperalgesia in wild-type mice, and thus, may have applications in the treatment of musculoskeletal pain in humans.

Indexed as

Acid Sensing Ion ChannelsAnimalsCHO CellsCricetinaeCricetulusDisease Models, AnimalGene TargetingGenetic TherapyHyperalgesiaInflammation MediatorsMaleMiceMice, Inbred C57BLMicroRNAsMusculoskeletal PainMyositisAcid Sensing Ion ChannelsASIC3 protein, mouseInflammation MediatorsMicroRNAsSodium Channels

Identifiers

PMID21843914
PMCPMC3476729
OpenAlexW1976488219

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.