Evidence map›Paper›PMID 28306605›Full record

ArticlePain2017

Hyperalgesic priming (type II) induced by repeated opioid exposure: maintenance mechanisms.

Dioneia Araldi, Luiz F Ferrari, Jon D Levine

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pain, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

33 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Article
  3. Sex differences in the transition to chronic pain.The Journal of clinical investigation · 2025
    Review
  4. Article
  5. Mu-Opioid Receptor (MOR) Dependence of Pain in Chemotherapy-Induced Peripheral Neuropathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. PI3Kγ/AKT Signaling in High Molecular Weight Hyaluronan (HMWH)-Induced Anti-Hyperalgesia and Reversal of Nociceptor Sensitization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  14. Article
  15. Article
  16. Review
  17. Opioid-Induced Hyperalgesic Priming in Single Nociceptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    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

3 authors at 1 institution in 1 country.

Dioneia AraldiDepartments of Medicine and Oral Surgery, and Division of Neuroscience, University of California, San Francisco, San Francisco, CA, USA.
Luiz F Ferrari
Jon D Levine
University of California, San Francisco · US

Funding

Nociceptor mechanisms in the transition from acute to chronic painR01NS084545 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEVINE, JON DAVID · 2014 to 2018
$3.1M
NINDS NIH HHS R01 NS084545
6 · The paper itself

Abstract

We previously developed a model of opioid-induced neuroplasticity in the peripheral terminal of the nociceptor that could contribute to opioid-induced hyperalgesia, type II hyperalgesic priming. Repeated administration of mu-opioid receptor (MOR) agonists, such as DAMGO, at the peripheral terminal of the nociceptor, induces long-lasting plasticity expressed, prototypically as opioid-induced hyperalgesia and prolongation of prostaglandin E2-induced hyperalgesia. In this study, we evaluated the mechanisms involved in the maintenance of type II priming. Opioid receptor antagonist, naloxone, induced hyperalgesia in DAMGO-primed paws. When repeatedly injected, naloxone-induced hyperalgesia, and hyperalgesic priming, supporting the suggestion that maintenance of priming involves changes in MOR signaling. However, the knockdown of MOR with oligodeoxynucleotide antisense did not reverse priming. Mitogen-activated protein kinase and focal adhesion kinase, which are involved in the Src signaling pathway, previously implicated in type II priming, also inhibited the expression, but not maintenance of priming. However, when Src and mitogen-activated protein kinase inhibitors were coadministered, type II priming was reversed, in male rats. A second model of priming, latent sensitization, induced by complete Freund's adjuvant was also reversed, in males. In females, the inhibitor combination was only able to inhibit the expression and maintenance of DAMGO-induced priming when knockdown of G-protein-coupled estrogen receptor 30 (GPR30) in the nociceptor was performed. These findings demonstrate that the maintenance of DAMGO-induced type II priming, and latent sensitization is mediated by an interaction between, Src and MAP kinases, which in females is GPR30 dependent.

Indexed as

NaloxoneNarcotic AntagonistsAnimalsEnkephalin, Ala(2)-MePhe(4)-Gly(5)-Enzyme InhibitorsFemaleGene Knockdown TechniquesHyperalgesiaMaleMAP Kinase Signaling SystemPain ThresholdRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReceptors, Opioid, muSex FactorsEnkephalin, Ala(2)-MePhe(4)-Gly(5)-Enzyme InhibitorsGper1 protein, ratNaloxoneNarcotic AntagonistsReceptors, G-Protein-CoupledReceptors, Opioid, mu

Identifiers

PMID28306605
PMCPMC5474187
OpenAlexW2595008877

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.