Evidence map›Paper›PMID 33834930›Full record

ArticleAutophagy2021

Combination of autophagy and NFE2L2/NRF2 activation as a treatment approach for neuropathic pain.

Jian Li, Mouli Tian, Tong Hua, Haowei Wang, Mei Yang, Wenqian Li, Xiaoping Zhang, Hongbin Yuan

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

Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
11.1field-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

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.

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9 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

8 authors at 2 institutions in 1 country.

Jian LiDepartment of Anesthesiology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China.
Mouli TianDepartment of Anesthesiology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China.
Tong HuaDepartment of Anesthesiology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China.
Haowei WangDepartment of Anesthesiology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China.
Mei YangDepartment of Anesthesiology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China.
Wenqian LiDepartment of Anesthesiology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China.
Xiaoping ZhangDepartment of Interventional & Vascular Surgery, Tongji University School of Medicine, Shanghai 200072, China.
Hongbin YuanDepartment of Anesthesiology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China.ORCID 0000-0001-8468-4005
Shanghai Changzheng Hospital · CNTongji University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Macroautophagy/autophagy, an evolutionarily conserved process, plays an important role in the regulation of immune inflammation and nervous system homeostasis. However, the exact role and mechanism of autophagy in pain is still unclear. Here, we showed that impaired autophagy flux mainly occurred in astrocytes during the maintenance of neuropathic pain. No matter the stage of neuropathic pain induction or maintenance, activation of autophagy relieved the level of pain, whereas inhibition of autophagy aggravated pain. Moreover, the levels of neuroinflammation and reactive oxygen species (ROS) were increased or decreased following autophagy inhibition or activation. Further study showed that inhibition of autophagy slowed the induction, but increased the maintenance of neuroinflammatory responses, which could be achieved by promoting the binding of TRAF6 (TNF receptor-associated factor 6) to K63 ubiquitinated protein, and increasing the levels of p-MAPK8/JNK (mitogen-activated protein kinase 8) and nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB/NF-κB). Impaired autophagy also reduced the protective effect of astrocytes on neurons against ROS stress because of the decrease in the level of glutathione released by astrocytes, which could be improved by activating the NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2) pathway. We also demonstrated that simultaneous activation of autophagy and the NFE2L2 pathway further relieved pain, compared to activating autophagy alone. Our study provides an underlying mechanism by which autophagy participates in the regulation of neuropathic pain, and a combination of autophagy and NFE2L2 activation may be a new treatment approach for neuropathic pain.

Indexed as

AutophagyNeuralgiaHumansKelch-Like ECH-Associated Protein 1MacroautophagyNF-E2-Related Factor 2Kelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2astrocytesAutophagyneuroinflammationneuronneuropathic painnfe2l2ros

Identifiers

PMID33834930
PMCPMC8726676
OpenAlexW3143477429

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.