Evidence map›Paper›PMID 29378191›Full record

ArticleEuropean journal of pharmacology2018

Involvement of the N/OFQ-NOP system in rat morphine antinociceptive tolerance: Are astrocytes the crossroad?

Laura Micheli, Elena Lucarini, Francesca Corti, Roberto Ciccocioppo, Girolamo Calò, Anna Rizzi, Carla Ghelardini, Lorenzo Di Cesare Mannelli

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in European journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 39% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Laura MicheliDepartment of Neuroscience, Psychology, Drug Research and Child Health - Neurofarba - Pharmacology and Toxicology Section, University of Florence, Florence, Italy.
Elena LucariniDepartment of Neuroscience, Psychology, Drug Research and Child Health - Neurofarba - Pharmacology and Toxicology Section, University of Florence, Florence, Italy.
Francesca CortiDepartment of Neuroscience, Psychology, Drug Research and Child Health - Neurofarba - Pharmacology and Toxicology Section, University of Florence, Florence, Italy.
Roberto CiccocioppoSchool of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
Girolamo CalòDepartment of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Italy.
Anna RizziDepartment of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Italy.
Carla GhelardiniDepartment of Neuroscience, Psychology, Drug Research and Child Health - Neurofarba - Pharmacology and Toxicology Section, University of Florence, Florence, Italy.
Lorenzo Di Cesare MannelliDepartment of Neuroscience, Psychology, Drug Research and Child Health - Neurofarba - Pharmacology and Toxicology Section, University of Florence, Florence, Italy. Electronic address: lorenzo.mannelli@unifi.it.
University of Florence · ITUniversity of Ferrara · ITUniversità di Camerino · IT

Funding

The Nociceptin ORL1 System: Treatment Target for RelapseR01AA014351 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI Friedbert Weiss · 2004 to 2026
$7.3M
NIAAA NIH HHS R01 AA014351
6 · The paper itself

Abstract

The development of tolerance to the antinociceptive effect is a main problem associated with the repeated administration of opioids. The progressively higher doses required to relieve pain reduce safety and exacerbate the side effects of classical opioid receptor agonists like morphine. Nociceptin/orphanin FQ (N/OFQ) and its NOP receptor constitute the fourth endogenous opioid system that is involved in the control of broad spectrum of biological functions, including pain transmission. Aim of this work was to evaluate the relevance of the N/OFQ-NOP system in morphine antinociceptive action and in the development of morphine tolerance in the rat. Continuous spinal intrathecal infusion of morphine (1-3 nmol/h) evoked analgesic effects for 5 days in wild type animals. The same doses infused in NOP(-/-) rats showed a lower analgesic efficacy, while the onset of tolerance was delayed to day 9. N/OFQ (1-3 nmol/h), continuously infused in NOP(+/+) animals, showed an analgesic profile similar to morphine. Immunohistochemical analysis of the dorsal horn of the spinal cord of morphine tolerant NOP(+/+) rats showed an increased number of Iba1- and GFAP-positive cells (microglia and astrocytes, respectively). Interestingly, microglia but not astrocyte activation was observed in NOP(-/-) morphine tolerant rat. A selective activation of astrocytes was observed in the dorsal horn of wild type N/OFQ tolerant rats. The antinociceptive effect of morphine partially depends by the N/OFQ-NOP system that participates in the development of morphine tolerance. In particular, NOP receptors are involved in morphine-induced astrocyte activation, and N/OFQ per se increases astrocyte density.

Indexed as

AnalgesicsAnimalsAstrocytesDose-Response Relationship, DrugMaleMorphineNociceptinOpioid PeptidesRatsAnalgesicsMorphineNociceptinOpioid PeptidesGlial cellsMorphine toleranceN/OFQNOP(-/-) ratsNOP receptor

Identifiers

PMID29378191
PMCPMC6064644
OpenAlexW2788279139

What OpenQuestion holds

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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.