Evidence map›Paper›PMID 22716933›Full record

ArticleJournal of neurochemistry2012

P-glycoprotein trafficking at the blood-brain barrier altered by peripheral inflammatory hyperalgesia.

Gwen McCaffrey, William D Staatz, Lucy Sanchez-Covarrubias, Jessica D Finch, Kristen Demarco, Mei-Li Laracuente, Patrick T Ronaldson, Thomas P Davis

Open access · greenAbstract read
In one paragraph

Article in Journal of neurochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

45 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Review
  3. Assessing Blood-brain Barrier Function in the Context of Pain Management.Central nervous system agents in medicinal chemistry · 2024
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Acute pain alters P-glycoprotein-containing protein complexes in rat cerebral microvessels: Implications for P-glycoprotein trafficking.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018
    Article
  16. Review
  17. Isolation of Cerebral Capillaries from Fresh Human Brain Tissue.Journal of visualized experiments : JoVE · 2018
    Article
  18. Article
  19. Review
  20. Article
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 1 institution in 1 country.

Gwen McCaffreyDepartment of Medical Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85745, USA. gwenm@email.arizona.edu
William D Staatz
Lucy Sanchez-Covarrubias
Jessica D Finch
Kristen Demarco
Mei-Li Laracuente
Patrick T Ronaldson
Thomas P Davis
University of Arizona · US

Funding

BLOOD BRAIN BARRIER CHANGES INDUCED BY PAINR01NS042652 · NINDS · UNIVERSITY OF ARIZONA · PI DAVIS, THOMAS PAUL · 2002 to 2017
$7.6M
BLOOD TO CNS UPTAKE OF OPIOID PEPTIDE DRUGSR01DA011271 · NIDA · UNIVERSITY OF ARIZONA · PI DAVIS, THOMAS PAUL · 1997 to 2014
$4.4M
HYPOXIC/AGLYCEMIC STRESS TO ENDOTHELIAL CELLS OF THE BLOR01NS039592 · NINDS · UNIVERSITY OF ARIZONA · PI DAVIS, THOMAS PAUL · 2000 to 2009
$3.1M
NCI NIH HHS CA 09820-0251NIDA NIH HHS R01 DA011271NIDA NIH HHS R01-DA12684NINDS NIH HHS R01 NS039592NINDS NIH HHS R01 NS042652NINDS NIH HHS R01-NS 39592NINDS NIH HHS R01-NS42652
6 · The paper itself

Abstract

P-glycoprotein (ABCB1/MDR1, EC 3.6.3.44), the major efflux transporter at the blood-brain barrier (BBB), is a formidable obstacle to CNS pharmacotherapy. Understanding the mechanism(s) for increased P-glycoprotein activity at the BBB during peripheral inflammatory pain is critical in the development of novel strategies to overcome the significant decreases in CNS analgesic drug delivery. In this study, we employed the λ-carrageenan pain model (using female Sprague-Dawley rats), combined with confocal microscopy and subcellular fractionation of cerebral microvessels, to determine if increased P-glycoprotein function, following the onset of peripheral inflammatory pain, is associated with a change in P-glycoprotein trafficking which leads to pain-induced effects on analgesic drug delivery. Injection of λ-carrageenan into the rat hind paw induced a localized, inflammatory pain (hyperalgesia) and simultaneously, at the BBB, a rapid change in colocalization of P-glycoprotein with caveolin-1, a key scaffolding/trafficking protein. Subcellular fractionation of isolated cerebral microvessels revealed that the bulk of P-glycoprotein constitutively traffics to membrane domains containing high molecular weight, disulfide-bonded P-glycoprotein-containing structures that cofractionate with membrane domains enriched with monomeric and high molecular weight, disulfide-bonded, caveolin-1-containing structures. Peripheral inflammatory pain promoted a dynamic redistribution between membrane domains of P-glycoprotein and caveolin-1. Disassembly of high molecular weight P-glycoprotein-containing structures within microvascular endothelial luminal membrane domains was accompanied by an increase in ATPase activity, suggesting a potential for functionally active P-glycoprotein. These results are the first observation that peripheral inflammatory pain leads to specific structural changes in P-glycoprotein responsible for controlling analgesic drug delivery to the CNS.

Indexed as

Adenosine TriphosphatasesAnimalsATP Binding Cassette Transporter, Subfamily B, Member 1Blood-Brain BarrierCarrageenanCaveolin 1Disease Models, AnimalFemaleHyperalgesiaMicrovesselsMolecular WeightNeurogenic InflammationProtein TransportRatsRats, Sprague-DawleyAdenosine TriphosphatasesATP Binding Cassette Transporter, Subfamily B, Member 1CarrageenanCaveolin 1

Identifiers

PMID22716933
PMCPMC3851298
OpenAlexW1637334016

What OpenQuestion holds

Textmetadata
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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.