Evidence map›Paper›PMID 23946412›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013

Protein kinase Cε is required for spinal analgesic synergy between delta opioid and alpha-2A adrenergic receptor agonist pairs.

Daniel J Schuster, Kelley F Kitto, Aaron C Overland, Robert O Messing, Laura S Stone, Carolyn A Fairbanks, George L Wilcox

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

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

12 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Alleviating pain with delta opioid receptor agonists: evidence from experimental models.Journal of neural transmission (Vienna, Austria : 1996) · 2020
    Review
  3. The Study of Pain in Rats and Mice.Comparative medicine · 2019
    Review
  4. Article
  5. Article
  6. Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016
    Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Analgesic synergy between opioid and α2 -adrenoceptors.British journal of pharmacology · 2015
    Review
  12. 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

7 authors at 5 institutions in 3 countries.

Daniel J SchusterDepartment of Neuroscience, Medical School, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Kelley F Kitto
Aaron C Overland
Robert O Messing
Laura S Stone
Carolyn A Fairbanks
George L Wilcox
University of Minnesota Medical Center · USInstitute of Pharmacology · CZMcGill University · CAThe University of Texas at Austin · USUniversity of California, San Diego · US

Funding

Receptors and Second Messengers for Pain and AnalgesiaP01NS053709 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MESSING, ROBERT O. · 2007 to 2011
$5.0M
Mechanisms of Opioid Receptor InteractionsR01DA015438 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI WILCOX, GEORGE LATIMER · 2004 to 2014
$3.3M
Regulation of GABAA Receptors by PKC epsilon.R01AA013588 · NIAAA · UNIVERSITY OF TEXAS AT AUSTIN · PI MESSING, ROBERT O. · 2002 to 2016
$1.9M
Gene Therapy in Chronic PainF31NS063634 · NINDS · UNIVERSITY OF MINNESOTA · PI SCHUSTER, DANIEL J. · 2009 to 2011
$95k
NIAAA NIH HHS R01 AA013588NIDA NIH HHS R01 DA015438NINDS NIH HHS F31 NS063634NINDS NIH HHS P01 NS053709
6 · The paper itself

Abstract

We recently showed that spinal synergistic interactions between δ opioid receptors (δORs) and α2A adrenergic receptors (α2AARs) require protein kinase C (PKC). To identify which PKC isoforms contribute to analgesic synergy, we evaluated the effects of various PKC-isoform-specific peptide inhibitors on synergy between δORs and α2AARs using the tail flick assay of thermal nociception in mice. Only a PKCε inhibitor abolished synergy between a δOR agonist and an α2AAR agonist. We tested a panel of combinations of opioid and adrenergic agonists in PKCε knock-out mice and found that all four combinations of a δOR agonist and an α2AAR agonist required PKCε for antinociceptive synergy. None of the combinations of a μOR agonist with an α2AR agonist required PKCε. Immunohistochemistry confirmed that PKCε could be found in the population of peptidergic primary afferent nociceptors where δORs and α2AARs have been found to extensively colocalize. Immunoreactivity for PKCε was found in the majority of dorsal root ganglion neurons and intensely labeled laminae I and II of the spinal cord dorsal horn. PKCε is widespread in the spinal nociceptive system and in peptidergic primary afferents it appears to be specifically involved in mediating the synergistic interaction between δORs and α2AARs.

Indexed as

Anesthesia, SpinalAdrenergic alpha-2 Receptor AgonistsAnalgesicsAnimalsBrimonidine TartrateClonidineDrug SynergismEnzyme InhibitorsFemaleImmunohistochemistryIsoenzymesMaleMiceMice, Inbred C57BLMice, KnockoutOligopeptidesAdrenergic alpha-2 Receptor AgonistsAnalgesicsBrimonidine TartrateClonidinedeltorphin II, Ala(2)-Enzyme InhibitorsIsoenzymesOligopeptidesProtein Kinase C-epsilonQuinoxalinesReceptors, Adrenergic, alpha-2Receptors, Opioid, delta

Identifiers

PMID23946412
PMCPMC3742937
OpenAlexW1985218639

What OpenQuestion holds

Textmetadata
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.