Evidence map›Paper›PMID 29576387›Full record

ArticleNeuron2018

Functional Divergence of Delta and Mu Opioid Receptor Organization in CNS Pain Circuits.

Dong Wang, Vivianne L Tawfik, Gregory Corder, Sarah A Low, Amaury François, Allan I Basbaum, Grégory Scherrer

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

Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
11.2field-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

91 citing papers in PubMed, 150 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Activation of µ-δ Opioid Receptor Heteromer Attenuates Chemotherapy-Induced Neuropathic Pain in Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Regulatory T cell-derived enkephalin gates nociception.bioRxiv : the preprint server for biology · 2024
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Optogenetic and Chemogenic Control of Pain Signaling: Molecular Markers.International journal of molecular sciences · 2023
    Review

31 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

7 authors at 4 institutions in 1 country.

Dong WangDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, CA 94304, USA; Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA 94304, USA; Department of Neurosurgery, Stanford University, Palo Alto, CA 94304, USA; Stanford Neurosciences Institute, Stanford University, Palo Alto, CA 94304, USA.
Vivianne L TawfikDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, CA 94304, USA; Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA 94304, USA; Department of Neurosurgery, Stanford University, Palo Alto, CA 94304, USA; Stanford Neurosciences Institute, Stanford University, Palo Alto, CA 94304, USA.
Gregory CorderDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, CA 94304, USA; Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA 94304, USA; Department of Neurosurgery, Stanford University, Palo Alto, CA 94304, USA; Stanford Neurosciences Institute, Stanford University, Palo Alto, CA 94304, USA.
Sarah A LowDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, CA 94304, USA; Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA 94304, USA; Department of Neurosurgery, Stanford University, Palo Alto, CA 94304, USA; Stanford Neurosciences Institute, Stanford University, Palo Alto, CA 94304, USA.
Amaury FrançoisDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, CA 94304, USA; Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA 94304, USA; Department of Neurosurgery, Stanford University, Palo Alto, CA 94304, USA; Stanford Neurosciences Institute, Stanford University, Palo Alto, CA 94304, USA.
Allan I BasbaumDepartment of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.
Grégory ScherrerDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, CA 94304, USA; Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA 94304, USA; Department of Neurosurgery, Stanford University, Palo Alto, CA 94304, USA; Stanford Neurosciences Institute, Stanford University, Palo Alto, CA 94304, USA; New York Stem Cell Foundation - Robertson Investigator, Stanford University, Palo Alto, CA 94304, USA. Electronic address: gs25@stanford.edu.
Stanford University · USNeurosciences Institute · USPalo Alto University · USUniversity of California, San Francisco · US

Funding

Interdisciplinary Research Training in Pain and Substance Use DisordersT32DA035165 · NIDA · STANFORD UNIVERSITY · PI SEAN C MACKEY · 2013 to 2026
$7.2M
From the spinal cord to the brain: Neurology of the pain and itch neuronsR35NS097306 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASBAUM, ALLAN I. · 2017 to 2024
$7.2M
Research in Anesthesia Training Program (ReAP)T32GM089626 · NIGMS · STANFORD UNIVERSITY · PI Vivianne L Tawfik · 2010 to 2026
$5.2M
Multiple Opioid Receptors and the Control of PainR01DA029204 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASBAUM, ALLAN I. · 2011 to 2015
$1.9M
Identification of cells and signaling mechanisms underlying opioid analgesia and side effectsR01DA044481 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SCHERRER, GREGORY · 2017 to 2021
$1.8M
Analgesic Mechanism of Action of Endogenous Opioid Peptides Enkephalins with a FoR00DA031777 · NIDA · STANFORD UNIVERSITY · PI SCHERRER, GREGORY · 2012 to 2014
$737k
Deconstructing the network mechanisms of chronic pain and reward in the amygdalaK99DA043609 · NIDA · STANFORD UNIVERSITY · PI CORDER, GREGORY · 2017 to 2018
$350k
Analgesic Mechanism of Action of Endogenous Opioid Peptides Enkephalins with a FoK99DA031777 · NIDA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SCHERRER, GREGORY · 2011 to 2011
$161k
Synaptic mechanisms of opioid-induced hyperalgesia and toleranceF32DA041029 · NIDA · STANFORD UNIVERSITY · PI CORDER, GREGORY · 2016 to 2016
$58k
NIDA NIH HHS F32 DA041029NIDA NIH HHS K99 DA031777NIDA NIH HHS K99 DA043609NIDA NIH HHS R00 DA031777NIDA NIH HHS R01 DA029204NIDA NIH HHS R01 DA044481NIDA NIH HHS T32 DA035165NIGMS NIH HHS T32 GM089626NINDS NIH HHS R35 NS097306
6 · The paper itself

Abstract

Cellular interactions between delta and mu opioid receptors (DORs and MORs), including heteromerization, are thought to regulate opioid analgesia. However, the identity of the nociceptive neurons in which such interactions could occur in vivo remains elusive. Here we show that DOR-MOR co-expression is limited to small populations of excitatory interneurons and projection neurons in the spinal cord dorsal horn and unexpectedly predominates in ventral horn motor circuits. Similarly, DOR-MOR co-expression is rare in parabrachial, amygdalar, and cortical brain regions processing nociceptive information. We further demonstrate that in the discrete DOR-MOR co-expressing nociceptive neurons, the two receptors internalize and function independently. Finally, conditional knockout experiments revealed that DORs selectively regulate mechanical pain by controlling the excitability of somatostatin-positive dorsal horn interneurons. Collectively, our results illuminate the functional organization of DORs and MORs in CNS pain circuits and reappraise the importance of DOR-MOR cellular interactions for developing novel opioid analgesics.

Indexed as

AnimalsAnterior Horn CellsCentral Nervous SystemMaleMice, Inbred C57BLMice, KnockoutNerve NetPainPain MeasurementPosterior Horn CellsReceptors, Opioid, deltaReceptors, Opioid, muReceptors, Opioid, deltaReceptors, Opioid, muanalgesiabrainco-expressiondistributionG protein-coupled inwardly rectifying potassium channelsinternalizationmu and delta opioid receptorsneuronspain neural circuitsspinal cord

Identifiers

PMID29576387
PMCPMC5896237
OpenAlexW2793110992

What OpenQuestion holds

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Registered trials

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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.