Evidence map›Paper›PMID 24631560›Full record

ArticleNeuroscience letters2014

Suppression of spinal connexin 43 expression attenuates mechanical hypersensitivity in rats after an L5 spinal nerve injury.

Qian Xu, Yong-Kwan Cheong, Shao-Qiu He, Vinod Tiwari, Jian Liu, Yun Wang, Srinivasa N Raja, Jinheng Li, Yun Guan, Weiyan Li

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

Article in Neuroscience letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Gap junctions, pannexins and pain.Neuroscience letters · 2019
    Review
  11. Connexin Hemichannels in Astrocytes: Role in CNS Disorders.Frontiers in molecular neuroscience · 2019
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Spinal Gap Junction Channels in Neuropathic Pain.The Korean journal of pain · 2015
    Review
  20. 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

10 authors at 3 institutions in 3 countries.

Qian Xu *Department of Clinical Pharmacology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
Yong-Kwan Cheong *Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Shao-Qiu HeDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Vinod TiwariDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Jian LiuDepartment of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
Yun WangDepartment of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Srinivasa N RajaDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Jinheng LiDepartment of Clinical Pharmacology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
Yun GuanDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Weiyan LiDepartment of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, China.
Johns Hopkins University · USNanjing General Hospital of Nanjing Military Command · CNCapital Medical University · CN

Funding

Mrgs as New Target for the Treatment of Neuropathic PainR01NS070814 · NINDS · JOHNS HOPKINS UNIVERSITY · PI GUAN, YUN · 2011 to 2020
$3.2M
NINDS NIH HHS NS70814NINDS NIH HHS R01 NS070814
6 · The paper itself

Abstract

Activation of spinal astrocytes may contribute to neuropathic pain. Adjacent astrocytes can make direct communication through gap junctions formed by connexin 43 (Cx43) in the central nervous system. Yet, the role of spinal astroglial gap junctions in neuropathic pain is not fully understood. Since Cx43 is the connexin isoform expressed preferentially in astrocytes in the spinal cord, we used a small interfering RNA (siRNA) approach to examine whether suppression of spinal Cx43 expression inhibits mechanical hypersensitivity in rats after an L5 spinal nerve ligation (SNL). SNL rats were administered intrathecal Cx43 siRNA (3μg/15μl, twice/day) or an equal amount of mismatch siRNA (control) on days 14-17 post-SNL. Cx43 siRNA, but not mismatch siRNA, alleviated mechanical hypersensitivity in SNL rats. Furthermore, Western blot analysis showed that the pain inhibition induced by Cx43 siRNA correlated with downregulation of Cx43 expression, but not that of Cx36 (the neuronal gap junction protein) or glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes) in the spinal cord of SNL rats. Western blot analysis and immunohistochemistry also showed that SNL increased GFAP expression, but decreased Cx43 expression, in spinal cord. Our results provide direct evidence that selective suppression of spinal Cx43 after nerve injury alleviates neuropathic mechanical hypersensitivity. These findings suggest that in the spinal cord, the enhanced function of astroglial gap junctions, especially those formed by Cx43, may be important to neuropathic pain in SNL rats.

Indexed as

AnimalsConnexin 43ConnexinsDown-RegulationGap Junction delta-2 ProteinGlial Fibrillary Acidic ProteinHyperalgesiaInjections, SpinalLumbosacral RegionMaleNeuralgiaRats, Sprague-DawleyRNA, MessengerRNA, Small InterferingSpinal CordSpinal NervesConnexin 43ConnexinsGap Junction delta-2 ProteinGja1 protein, ratGlial Fibrillary Acidic ProteinRNA, MessengerRNA, Small InterferingConnexin 43Gap junctionGliaNeuropathic pain

Identifiers

PMID24631560
PMCPMC4007756
OpenAlexW2060303567

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.