Evidence map›Paper›PMID 29500928›Full record

ArticleBritish journal of pharmacology2018

Exchange factor directly activated by cAMP-PKCε signalling mediates chronic morphine-induced expression of purine P2X3 receptor in rat dorsal root ganglia.

Wenying Wang, Xiaqing Ma, Limin Luo, Min Huang, Jing Dong, Xiaoli Zhang, Wei Jiang, Tao Xu

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

Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

9 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Role of EPAC1 in chronic pain.Biochemistry and biophysics reports · 2024
    Review
  4. Article
  5. Article
  6. 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

8 authors at 1 institution in 1 country.

Wenying WangDepartment of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Xiaqing MaDepartment of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Limin LuoDepartment of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Min HuangDepartment of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Jing DongDepartment of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Xiaoli ZhangDepartment of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Wei JiangDepartment of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Tao XuDepartment of Anesthesiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.ORCID 0000-0001-5868-4079
Shanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeThe P2X3 receptor is a major receptor in the processing of nociceptive information in dorsal root ganglia. We investigated the role of the P2X3 receptor and the detailed mechanisms underlying chronic morphine-induced analgesic tolerance in rats. EXPERIMENTAL APPROACH: Repeated i.t. morphine treatment was used to induce anti-nociceptive tolerance. The expression of spinal P2X3 receptor, phosphorylated PKCε and exchange factor directly activated by cAMP (Epac) were evaluated. Effects of A-317491 (P2X3 antagonist), ε-V1-2 (PKCε inhibitor) and ESI-09 (Epac inhibitor) on mechanical pain thresholds and tail-flick latency after chronic morphine treatment were determined. Co-localization of P2X3 receptor with NeuNs (marker of neuron), IB4 (marker of small DRG neurons), peripherin, PKCε and Epac were performed by double immunofluorescence staining. KEY

resultsChronic morphine time-dependently increased the expression of P2X3 receptor, phosphorylated PKCε and Epac in DRGs. ε-V1-2 prevented chronic morphine-induced expression of P2X3 receptor. ESI-09 decreased the phosphorylation of PKCε and up-regulated expression of Epac after chronic morphine exposure. Mechanical pain thresholds and tail-flick latency showed that A317491, ε-V1-2 and ESI-09 significantly attenuated the loss of morphine's analgesic potency. Morphine-induced P2X3 receptor expression mainly occurred in neurons staining for IB4 and peripherin. Co-localization of P2X3 receptor with PKCε and Epac was demonstrated in the same neurons. CONCLUSIONS AND IMPLICATIONS: Chronic morphine exposure increased the expression of P2X3 receptor, and i.t. P2X3 receptor antagonists attenuated the loss of morphine's analgesic effect. Inhibiting Epac/PKCε signalling was shown to play a significant inhibitory role in chronic morphine-induced P2X3 receptor expression and attenuate morphine-induced tolerance.

Indexed as

AnalgesicsAnimalsCyclic AMPGanglia, SpinalGuanine Nucleotide Exchange FactorsMaleMorphineProtein Kinase C-epsilonRatsRats, Sprague-DawleyReceptors, Purinergic P2X3Signal TransductionAnalgesicsCyclic AMPGuanine Nucleotide Exchange FactorsMorphineProtein Kinase C-epsilonReceptors, Purinergic P2X3

Identifiers

PMID29500928
PMCPMC5913404
OpenAlexW2799954306

What OpenQuestion holds

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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.