Evidence map›Paper›PMID 29386025›Full record

ArticleJournal of neuroinflammation2018

miRNA-23a/CXCR4 regulates neuropathic pain via directly targeting TXNIP/NLRP3 inflammasome axis.

Zhiqiang Pan, Qun Shan, Pan Gu, Xiao Min Wang, Lydia Wai Tai, Menglan Sun, Xin Luo, Liting Sun, Chi Wai Cheung

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed, 2 pooled it
10.7field-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

111 citing papers in PubMed, 2 syntheses or guidelines pooled it, 184 citations in OpenAlex.

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  17. Biosynthesis inhibition of miR-142-5p in a NCellular & molecular biology letters · 2025
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51 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

9 authors at 2 institutions in 2 countries.

Zhiqiang PanJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, 221002, China. zhiqiangp2002@aliyun.com.
Qun ShanLaboratory and Clinical Research Institute for Pain, Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China.
Pan GuLaboratory and Clinical Research Institute for Pain, Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China.
Xiao Min WangLaboratory and Clinical Research Institute for Pain, Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China.
Lydia Wai TaiLaboratory and Clinical Research Institute for Pain, Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China.
Menglan SunJiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, 221002, China.
Xin LuoLaboratory and Clinical Research Institute for Pain, Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China.
Liting SunLaboratory and Clinical Research Institute for Pain, Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China.
Chi Wai CheungLaboratory and Clinical Research Institute for Pain, Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China. cheucw@hku.hk.
University of Hong Kong · HKXuzhou Medical College · CN

Funding

National Natural Science Foundation of China 81671096
6 · The paper itself

Abstract

backgroundChemokine CXC receptor 4 (CXCR4) in spinal glial cells has been implicated in neuropathic pain. However, the regulatory cascades of CXCR4 in neuropathic pain remain elusive. Here, we investigated the functional regulatory role of miRNAs in the pain process and its interplay with CXCR4 and its downstream signaling.

methodsmiRNAs and CXCR4 and its downstream signaling molecules were measured in the spinal cords of mice with sciatic nerve injury via partial sciatic nerve ligation (pSNL). Immunoblotting, immunofluorescence, immunoprecipitation, and mammal two-hybrid and behavioral tests were used to explore the downstream CXCR4-dependent signaling pathway.

resultsCXCR4 expression increased in spinal glial cells of mice with pSNL-induced neuropathic pain. Blocking CXCR4 alleviated the pain behavior; contrarily, overexpressing CXCR4 induced pain hypersensitivity. MicroRNA-23a-3p (miR-23a) directly bounds to 3' UTR of CXCR4 mRNA. pSNL-induced neuropathic pain significantly reduced mRNA expression of miR-23a. Overexpression of miR-23a by intrathecal injection of miR-23a mimics or lentivirus reduced spinal CXCR4 and prevented pSNL-induced neuropathic pain. In contrast, knockdown of miR-23a by intrathecal injection of miR-23a inhibitor or lentivirus induced pain-like behavior, which was reduced by CXCR4 inhibition. Additionally, miR-23a knockdown or CXCR4 overexpression in naïve mice could increase the thioredoxin-interacting protein (TXNIP), which was associated with induction of NOD-like receptor protein 3 (NLRP3) inflammasome. Indeed, CXCR4 and TXNIP were co-expressed. The mammal two-hybrid assay revealed the direct interaction between CXCR4 and TXNIP, which was increased in the spinal cord of pSNL mice. In particular, inhibition of TXNIP reversed pain behavior elicited by pSNL, miR-23a knockdown, or CXCR4 overexpression. Moreover, miR-23a overexpression or CXCR4 knockdown inhibited the increase of TXNIP and NLRP3 inflammasome in pSNL mice.

conclusionsmiR-23a, by directly targeting CXCR4, regulates neuropathic pain via TXNIP/NLRP3 inflammasome axis in spinal glial cells. Epigenetic interventions against miR-23a, CXCR4, or TXNIP may potentially serve as novel therapeutic avenues in treating peripheral nerve injury-induced nociceptive hypersensitivity.

Indexed as

AnimalsCarrier ProteinsHEK293 CellsHumansInflammasomesInjections, SpinalMaleMiceMice, Inbred C57BLMicroRNAsNeuralgiaNLR Family, Pyrin Domain-Containing 3 ProteinReceptors, CXCR4ThioredoxinsCarrier ProteinsCXCR4 protein, mouseInflammasomesMicroRNAsMirn23b microRNA, mouseNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseReceptors, CXCR4ThioredoxinsTxnip protein, mouseCXCR4miRNA-23aNLRP3 inflammasomeSciatic nerve injurySpinal glia cellTXNIP

Identifiers

PMID29386025
PMCPMC5791181
OpenAlexW2786315758

What OpenQuestion holds

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LicenceCC BY
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.