Evidence map›Paper›PMID 30746765›Full record

ArticleGlia2019

LRP1 deficiency in microglia blocks neuro-inflammation in the spinal dorsal horn and neuropathic pain processing.

Coralie Brifault, HyoJun Kwon, Wendy M Campana, Steven L Gonias

Open access · greenAbstract read
In one paragraph

Article in Glia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 8% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Pooled it
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  5. Review
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  12. Peripheral and central pathogenesis of postherpetic neuralgia.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2024
    Review
  13. Review
  14. Article
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  18. α1-Antitrypsin derived SP16 peptide demonstrates efficacy in rodent models of acute and neuropathic pain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  19. Article
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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

4 authors at 1 institution in 1 country.

Coralie BrifaultDepartment of Pathology, University of California San Diego, La Jolla, California.ORCID 0000-0002-9831-4491
HyoJun KwonDepartment of Anesthesiology, University of California San Diego, La Jolla, California.
Wendy M CampanaDepartment of Anesthesiology, University of California San Diego, La Jolla, California.ORCID 0000-0002-9039-1396
Steven L GoniasDepartment of Pathology, University of California San Diego, La Jolla, California.
University of California San Diego · US

Funding

Regulation of Inflammation by the Fibrinolytic SystemR01HL136395 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GONIAS, STEVEN L. · 2017 to 2025
$3.5M
Schwann Cell NMDA Receptor in PNS InjuryR01NS097590 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CAMPANA, WENDY M., GONIAS, STEVEN L. · 2017 to 2020
$1.4M
Identifying novel proteins in injured nerves that promote functional regenerationI01RX002484 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI CAMPANA, WENDY M. · 2019 to 2021
–
NHLBI NIH HHS R01 HL136395NINDS NIH HHS R01 NS097590RRD VA I01 RX002484
6 · The paper itself

Abstract

Following injury to the peripheral nervous system (PNS), microglia in the spinal dorsal horn (SDH) become activated and contribute to the development of local neuro-inflammation, which may regulate neuropathic pain processing. The molecular mechanisms that control microglial activation and its effects on neuropathic pain remain incompletely understood. We deleted the gene encoding the plasma membrane receptor, LDL Receptor-related Protein-1 (LRP1), conditionally in microglia using two distinct promoter-Cre recombinase systems in mice. LRP1 deletion in microglia blocked development of tactile allodynia, a neuropathic pain-related behavior, after partial sciatic nerve ligation (PNL). LRP1 deletion also substantially attenuated microglial activation and pro-inflammatory cytokine expression in the SDH following PNL. Because LRP1 shedding from microglial plasma membranes generates a highly pro-inflammatory soluble product, we demonstrated that factors which activate spinal cord microglia, including lipopolysaccharide (LPS) and colony-stimulating factor-1, promote LRP1 shedding. Proteinases known to mediate LRP1 shedding, including ADAM10 and ADAM17, were expressed at increased levels in the SDH after PNL. Furthermore, LRP1-deficient microglia in cell culture expressed significantly decreased levels of interleukin-1β and interleukin-6 when treated with LPS. We conclude that in the SDH, microglial LRP1 plays an important role in establishing and/or amplifying local neuro-inflammation and neuropathic pain following PNS injury. The responsible mechanism most likely involves proteolytic release of LRP1 from the plasma membrane to generate a soluble product that functions similarly to pro-inflammatory cytokines in mediating crosstalk between cells in the SDH and in regulating neuropathic pain.

Indexed as

AnimalsInflammationLow Density Lipoprotein Receptor-Related Protein-1MaleMiceMice, Inbred C57BLMice, TransgenicMicrogliaNeuralgiaPain PerceptionSpinal Cord Dorsal HornLow Density Lipoprotein Receptor-Related Protein-1Lrp1 protein, mousecentral sensitizationLRP1membrane protein sheddingmicroglianeuropathic pain

Identifiers

PMID30746765
PMCPMC6462253
OpenAlexW2912433752

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.