Evidence map›Paper›PMID 29178967›Full record

ArticleJournal of neuroinflammation2017

Blocking ATP-sensitive potassium channel alleviates morphine tolerance by inhibiting HSP70-TLR4-NLRP3-mediated neuroinflammation.

Jie Qu, Xue-You Tao, Peng Teng, Yan Zhang, Ci-Liang Guo, Liang Hu, Yan-Ning Qian, Chun-Yi Jiang, Wen-Tao Liu

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

Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
3.4field-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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Recent insights into HSP70: proteostasis and beyond.Frontiers in molecular biosciences · 2026
    Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  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

9 authors at 2 institutions in 1 country.

Jie QuNeuroprotective Drug Discovery Key Laboratory of Nanjing Medical University, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Xue-You TaoNeuroprotective Drug Discovery Key Laboratory of Nanjing Medical University, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Peng TengNeuroprotective Drug Discovery Key Laboratory of Nanjing Medical University, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Yan ZhangNeuroprotective Drug Discovery Key Laboratory of Nanjing Medical University, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Ci-Liang GuoNeuroprotective Drug Discovery Key Laboratory of Nanjing Medical University, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Liang HuNeuroprotective Drug Discovery Key Laboratory of Nanjing Medical University, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Yan-Ning QianDepartment of Anesthesiology, 1st Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Chun-Yi JiangNeuroprotective Drug Discovery Key Laboratory of Nanjing Medical University, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China. jcy@njmu.edu.cn.
Wen-Tao LiuNeuroprotective Drug Discovery Key Laboratory of Nanjing Medical University, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China. painresearch@njmu.edu.cn.
Nanjing Medical University · CNChina Pharmaceutical University · CN

Funding

National Natural Science Foundation of China 81171044National Natural Science Foundation of China 81202513National Natural Science Foundation of China 81471142National Science Foundation for Young Scientists of Jiangsu province BK20161033
6 · The paper itself

Abstract

backgroundLong-term use of morphine induces analgesic tolerance, which limits its clinical efficacy. Evidence indicated morphine-evoked neuroinflammation mediated by toll-like receptor 4 (TLR4) - NOD-like receptor protein 3 (NLRP3) inflammasome was important for morphine tolerance. In our study, we investigated whether other existing alternative pathways caused morphine-induced activation of TLR4 in microglia. We focused on heat shock protein 70 (HSP70), a damage-associated molecular pattern (DAMP), which was released from various cells upon stimulations under the control of K

methodsCD-1 mice were used for tail-flick test to evaluate morphine tolerance. The microglial cell line BV-2 and neural cell line SH-SY5Y were used to investigate the pharmacological effects and the mechanism of glibenclamide on morphine-induced neuroinflammation. The activation of microglia was accessed by immunofluorescence staining. Neuroinflammation-related cytokines were measured by western blot and real-time PCR. The level of HSP70 and related signaling pathway were evaluated by western blot and immunofluorescence staining.

resultsMorphine induced the release of HSP70 from neurons. The released HSP70 activated microglia and triggered TLR4-mediated inflammatory response, leading to the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 and the activation of NLRP3 inflammasome. Moreover, anti-HSP70 neutralizing antibody partly attenuated chronic morphine tolerance. The secretion of HSP70 was under the control of MOR/AKT/K

conclusionsOur study indicated that morphine-induced extracellular HSP70 was an alternative way for the activation of TLR4-NLRP3 in analgesic tolerance. The release of HSP70 was regulated by MOR/AKT/K

Indexed as

MorphineAnimalsDrug ToleranceGlyburideHSP70 Heat-Shock ProteinsInflammasomesKATP ChannelsMiceNLR Family, Pyrin Domain-Containing 3 ProteinSignal TransductionToll-Like Receptor 4GlyburideHSP70 Heat-Shock ProteinsInflammasomesKATP ChannelsMorphineNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseTlr4 protein, mouseToll-Like Receptor 4HSP70KATP channelMorphine toleranceNeuroinflammationTLR4

Identifiers

PMID29178967
PMCPMC5702153
OpenAlexW2769423160

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.