Evidence map›Paper›PMID 23831863›Full record

ArticlePain2013

Chemokine contribution to neuropathic pain: respective induction of CXCL1 and CXCR2 in spinal cord astrocytes and neurons.

Zhi-Jun Zhang, De-Li Cao, Xin Zhang, Ru-Rong Ji, Yong-Jing Gao

Open access · greenAbstract read
In one paragraph

Article in Pain, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
155citing papers in PubMed, 1 pooled it
10.2field-weighted citation impact, top 1% 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

155 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Glial cells in neuropathic pain.Physiological reviews · 2026
    Review
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  14. Redox report : communications in free radical research · 2025
    Article
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  19. Article
  20. [Mechanisms of spinal microglia and astrocytes in exercise-induced analgesia].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Review

95 more citing papers are in PubMed but not listed here.

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 2 countries.

Zhi-Jun ZhangInstitute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China Department of Anatomy, Medical School of Nantong University, Nantong 226001, China Sensory Plasticity Laboratory, Department of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
De-Li Cao
Xin Zhang
Ru-Rong Ji
Yong-Jing Gao
Nantong University · CNDuke Medical Center · US

Funding

Neuronal and glial interactions of neuropathic painR01DE017794 · NIDCR · DUKE UNIVERSITY · PI BUCHHEIT, THOMAS · 2006 to 2021
$6.6M
Resolvins, protectins, and chronic pain resolution.R01NS067686 · NINDS · DUKE UNIVERSITY · PI JI, RU-RONG, SERHAN, CHARLES NICHOLAS · 2009 to 2013
$2.8M
Hemichannels, Astrocytic Release, and Neuropathic PainR01DE022743 · NIDCR · DUKE UNIVERSITY · PI JI, RU-RONG, NEDERGAARD, MAIKEN · 2012 to 2016
$2.0M
NIDCR NIH HHS DE17794NIDCR NIH HHS DE22743NIDCR NIH HHS R01 DE017794NIDCR NIH HHS R01 DE022743NINDS NIH HHS R01 NS067686
6 · The paper itself

Abstract

Recent studies have indicated an important role of chemokines such as CCL2 in the development of chronic pain. However, the distinct roles of different chemokines in the development and maintenance of neuropathic pain and in their interactions with neurons have not been clearly elucidated. We found that spinal nerve ligation (SNL) not only induced persistent neuropathic pain symptoms, including mechanical allodynia and heat hyperalgesia, but also produced sustained CXCL1 upregulation in the spinal cord. Double staining of immunofluorescence and in situ hybridization revealed that CXCL1 was primarily induced in spinal astrocytes. In cultured astrocytes, tumor necrosis factor-α induced robust CXCL1 expression via the activation of the c-jun N-terminal kinase. Intrathecal administration of CXCL1 neutralizing antibody transiently reduced SNL-induced pain hypersensitivity, suggesting an essential role of CXCL1 in neuropathic pain sensitization. In particular, intraspinal delivery of CXCL1 shRNA lentiviral vectors, either before or after SNL, persistently attenuated SNL-induced pain hypersensitivity. Spinal application of CXCL1 not only elicited pain hypersensitivity but also induced rapid neuronal activation, as indicated by the expression of phosphorylated extracellular signal-regulated kinase and cAMP response element binding protein, and c-Fos in spinal cord neurons. Interestingly, CXCR2, the primary receptor of CXCL1, was upregulated in dorsal horn neurons after SNL, and the CXCR2 antagonist SB225002 completely blocked the CXCL1-induced heat hyperalgesia. SB225002 also attenuated SNL-induced pain hypersensitivity. Collectively, our results have demonstrated a novel form of chemokine-mediated glial-neuronal interaction in the spinal cord that can drive neuropathic pain. Inhibition of the CXCL1-CXCR2 signaling may offer a new therapy for neuropathic pain management.

Indexed as

AnimalsAnimals, NewbornAstrocytesCells, CulturedChemokine CXCL1MaleMice, Inbred ICRNeuralgiaNeuronsReceptors, Interleukin-8BSpinal CordUp-RegulationChemokine CXCL1Cxcl1 protein, mouseReceptors, Interleukin-8BAstrocytesChemokinesCXCL1CXCR2Neuron–glia interactionNeuropathic pain

Identifiers

PMID23831863
PMCPMC3899784
OpenAlexW2040286122

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.