Evidence map›Paper›PMID 24726382›Full record

ArticleNeuron2014

Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord.

Adam P Kardon, Erika Polgár, Junichi Hachisuka, Lindsey M Snyder, Darren Cameron, Sinead Savage, Xiaoyun Cai, Sergei Karnup, Christopher R Fan, Gregory M Hemenway and 10 more

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

Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers.

0numbers the graph read from it
0cells of the map it votes in
201citing papers in PubMed
31.0field-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

201 citing papers in PubMed, 359 citations in OpenAlex.

  1. Trial
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  13. Skin innervation and itsFrontiers in cellular neuroscience · 2026
    Review
  14. Review
  15. Article
  16. Nalfurafine is Aversive at Antinociceptive Doses in Mice.Pharmacology research & perspectives · 2025
    Article
  17. Central neural circuits underlying itch sensation.Nature reviews. Neuroscience · 2025
    Review
  18. Article
  19. Article
  20. Article

141 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 6 institutions in 4 countries.

Adam P KardonDepartment of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
Erika PolgárInstitute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Junichi HachisukaDepartment of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
Lindsey M SnyderDepartment of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
Darren CameronInstitute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Sinead SavageInstitute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Xiaoyun CaiDepartment of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
Sergei KarnupDepartment of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
Christopher R FanDepartment of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
Gregory M HemenwayDepartment of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
Carcha S BernardDepartment of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
Erica S SchwartzUniversity of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; Department of Anesthesiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Hiroshi NagaseInternational Institute for Integrative Sleep Medicine, University of Tsukuba, Life Science Center of Tsukuba Advanced Research Alliance C-1F, 1-1-1 Tenoudai Tsukuba Ibaraki, Tsukuba 305-8577, Japan.
Christoph SchwarzerDepartment of Pharmacology, Innsbruck Medical University, A-6020 Innsbruck, Austria.
Masahiko WatanabeDepartment of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
Takahiro FurutaDepartment of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Takeshi KanekoDepartment of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
H Richard KoerberDepartment of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA.
Andrew J ToddInstitute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. Electronic address: andrew.todd@glasgow.ac.uk.
Sarah E RossDepartment of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; Department of Anesthesiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Electronic address: saross@pitt.edu.
University of Pittsburgh · USUniversity of Glasgow · GBKyoto University · JPHokkaido University · JPInnsbruck Medical University · ATTsukuba International University · JP

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
Investigating the Neural Circuits of ItchR01AR063772 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI H Richard Koerber, Sarah Elizabeth Ross · 2013 to 2026
$6.9M
Peripheral Nerve Regeneration and Sensory Neuron PlasticityR01NS023725 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KOERBER, H RICHARD · 1986 to 2017
$5.9M
Temple University Minority Access to Research Careers (MARC) programT34GM087239 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI TANAKA, JACQUELINE C · 2009 to 2018
$5.2M
Training in Mechanisms and Clinical Presentation of PainT32NS073548 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jami Lynn Saloman, BRADLEY K. TAYLOR · 2012 to 2026
$3.1M
Using dual intersectional genetics to understand and modulate itchR21AR064445 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ROSS, SARAH ELIZABETH · 2013 to 2014
$358k
Biotechnology and Biological Sciences Research Council BB/J001082Medical Research Council MR/L003430/1NCATS NIH HHS UL1 TR000005NIAMS NIH HHS R01 AR063772NIAMS NIH HHS R21 AR064445NIGMS NIH HHS T34 GM087239NINDS NIH HHS R01 NS023725NINDS NIH HHS T32 NS073548Wellcome Trust
6 · The paper itself

Abstract

Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5(-/-) mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we characterize B5-I neurons and show that they belong to a neurochemically distinct subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and show that dynorphin, which is released from B5-I neurons, is a key neuromodulator of pruritus. Finally, we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by menthol. These findings provide a cellular basis for the inhibition of itch by chemical counterstimuli and suggest that kappa opioids may be a broadly effective therapy for pathological itch.

Indexed as

Analgesics, OpioidAnimalsCapsaicinDynorphinsInterneuronsMaleMiceMice, Inbred C57BLMice, KnockoutNeural InhibitionOctreotideOrgan Culture TechniquesPosterior Horn CellsPruritusReceptors, Opioid, kappaSpinal CordAnalgesics, OpioidCapsaicinDynorphinsOctreotideReceptors, Opioid, kappa

Identifiers

PMID24726382
PMCPMC4022838
OpenAlexW2163039776

What OpenQuestion holds

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LicenceCC BY
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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.