Evidence map›Paper›PMID 26634308›Full record

ArticleNature communications2015

Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7.

Michael S Minett, Vanessa Pereira, Shafaq Sikandar, Ayako Matsuyama, Stéphane Lolignier, Alexandros H Kanellopoulos, Flavia Mancini, Gian D Iannetti, Yury D Bogdanov, Sonia Santana-Varela and 6 more

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

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 2 pooled it
12.6field-weighted citation impact, top 1% 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

97 citing papers in PubMed, 2 syntheses or guidelines pooled it, 186 citations in OpenAlex.

  1. Pooled it
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  7. Targeting NaInternational journal of molecular sciences · 2026
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37 more citing papers are in PubMed but not listed here.

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

16 authors at 1 institution in 1 country.

Michael S MinettMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
Vanessa PereiraMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
Shafaq SikandarMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
Ayako MatsuyamaMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
Stéphane LolignierMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
Alexandros H KanellopoulosMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
Flavia ManciniDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Gian D IannettiDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Yury D BogdanovMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
Sonia Santana-VarelaMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
Queensta MilletMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
Giorgios BaskozosInstitute of Structural and Molecular Biology, UCL, London WC1E 6BT, UK.
Raymond MacAllisterDepartment of Medicine, UCL, London WC1E 6BT, UK.
James J CoxMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
Jing ZhaoMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
John N WoodMolecular Nociception Group, WIBR, University College London, Gower Street, London WC1E 6BT, UK.
University College London · GB

Funding

Biotechnology and Biological Sciences Research Council BB/F000227/1Medical Research Council G0901905Medical Research Council G1100340Wellcome Trust 101054
6 · The paper itself

Abstract

Loss-of-function mutations in the SCN9A gene encoding voltage-gated sodium channel Nav1.7 cause congenital insensitivity to pain in humans and mice. Surprisingly, many potent selective antagonists of Nav1.7 are weak analgesics. We investigated whether Nav1.7, as well as contributing to electrical signalling, may have additional functions. Here we report that Nav1.7 deletion has profound effects on gene expression, leading to an upregulation of enkephalin precursor Penk mRNA and met-enkephalin protein in sensory neurons. In contrast, Nav1.8-null mutant sensory neurons show no upregulated Penk mRNA expression. Application of the opioid antagonist naloxone potentiates noxious peripheral input into the spinal cord and dramatically reduces analgesia in both female and male Nav1.7-null mutant mice, as well as in a human Nav1.7-null mutant. These data suggest that Nav1.7 channel blockers alone may not replicate the analgesic phenotype of null mutant humans and mice, but may be potentiated with exogenous opioids.

Indexed as

AdultAnimalsEnkephalinsFemaleHumansMaleMiceMice, KnockoutNAV1.7 Voltage-Gated Sodium ChannelPain Insensitivity, CongenitalSensationSensory Receptor CellsEnkephalinsNAV1.7 Voltage-Gated Sodium ChannelScn9a protein, mouse

Identifiers

PMID26634308
PMCPMC4686868
OpenAlexW2185789127

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.