Evidence map›Paper›PMID 21571003›Full record

ArticleJournal of neuroscience methods2011

Intrathecal PKA-selective siRNA treatment blocks sustained morphine-mediated pain sensitization and antinociceptive tolerance in rats.

S Tumati, W R Roeske, T M Largent-Milnes, T W Vanderah, E V Varga

Abstract readComparative Study
In one paragraph

Article in Journal of neuroscience methods, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

13 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Opioid Modulation of the Gut-Brain Axis in Opioid-Associated Comorbidities.Cold Spring Harbor perspectives in medicine · 2021
    Review
  6. Small-Conductance CaFrontiers in pharmacology · 2018
    Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Pain after discontinuation of morphine treatment is associated with synaptic increase of GluA4-containing AMPAR in the dorsal horn of the spinal cord.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013
    Article
  12. Cdk5: An Emerging Kinase in Pain Signaling.Brain disorders & therapy · 2013
    Article
  13. 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

5 authors at 1 institution in 1 country.

S TumatiDepartment of Pharmacology, The University of Arizona, Tucson, AZ 85724, USA.
W R Roeske
T M Largent-Milnes
T W Vanderah
E V Varga
University of Arizona · US

Funding

THERAPEUTIC PROFILES OF OPIOID DELTA RECEPTORS--NEW MODALITIESP01DA006284 · NIDA · UNIVERSITY OF ARIZONA · PI HRUBY, VICTOR J · 1989 to 2015
$14.8M
NOVEL NON-PEPTIDE OPIOID LIGANDS FOR PAINR01DA013449 · NIDA · UNIVERSITY OF ARIZONA · PI HRUBY, VICTOR J · 2000 to 2015
$6.8M
MOLECULAR MECHANISM OF ADENYLYL CYCLASE SUPERACTIVATIONR01GM065465 · NIGMS · UNIVERSITY OF ARIZONA · PI YAMAMURA, HENRY I · 2003 to 2006
$1.1M
NIDA NIH HHS DA06284NIDA NIH HHS P01 DA006284NIDA NIH HHS R01 DA013449NIGMS NIH HHS GM 065465NIGMS NIH HHS R01 GM065465
6 · The paper itself

Abstract

Sustained morphine treatment has been shown to produce paradoxical pain sensitization (opioid-induced hyperalgesia) and also causes increase in spinal pain neurotransmitter, such as calcitonin gene related peptide (CGRP), concentration in experimental animals. Studies have also shown that cyclic adenosine-monophosphate (cAMP)-dependent protein kinase (PKA) plays a major role in the regulation of presynaptic neurotransmitter (such as CGRP and substance P) synthesis and release. We have previously shown that in cultured primary sensory dorsal root ganglion (DRG) neurons sustained in vitro opioid agonist treatment upregulates cAMP levels (adenylyl cyclase (AC) superactivation) and augments basal and capsaicin evoked CGRP release in a PKA dependent manner. In the present study, we investigated the in vivo role of PKA in sustained morphine-mediated pain sensitization. Our data indicate that selective knock-down of spinal PKA activity by intrathecal (i.th.) pretreatment of rats with a PKA-selective small interference RNA (siRNA) mixture significantly attenuates sustained morphine-mediated augmentation of spinal CGRP immunoreactivity, thermal hyperalgesia, mechanical allodynia and antinociceptive tolerance. The present findings indicate that sustained morphine-mediated activation of spinal cAMP/PKA-dependent signaling may play an important role in opioid induced hyperalgesia.

Indexed as

RNA InterferenceAnimalsCalcitonin Gene-Related PeptideCapsaicinCyclic AMPCyclic AMP-Dependent Protein KinasesGenetic TherapyHot TemperatureHyperalgesiaInjections, SpinalMaleMorphineNarcoticsPosterior Horn CellsPresynaptic TerminalsRatsCalcitonin Gene-Related PeptideCapsaicinCyclic AMPCyclic AMP-Dependent Protein KinasesMorphineNarcoticsRNA, Small Interfering

Identifiers

PMID21571003
PMCPMC3120016
OpenAlexW2063375700

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.