Evidence map›Paper›PMID 34312228›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Estrogens influence female itch sensitivity via the spinal gastrin-releasing peptide receptor neurons.

Keiko Takanami, Daisuke Uta, Ken Ichi Matsuda, Mitsuhiro Kawata, Earl Carstens, Tatsuya Sakamoto, Hirotaka Sakamoto

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

11 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Elucidating the Multi-Target Anti-Pruritic Mechanism ofCurrent issues in molecular biology · 2026
    Article
  3. Article
  4. Article
  5. Estrogen alleviates acute and chronic itch in mice.Experimental and therapeutic medicine · 2023
    Article
  6. Article
  7. Article
  8. Article
  9. Footedness for scratching itchy eyes in rodents.Proceedings. Biological sciences · 2022
    Article
  10. Article
  11. Involvement of Histamine HInternational journal of molecular sciences · 2022
    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

7 authors at 5 institutions in 2 countries.

Keiko TakanamiUshimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University, Setouchi 701-4303, Japan; takanami@nig.ac.jp.ORCID 0000-0002-5462-1182
Daisuke UtaDepartment of Applied Pharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
Ken Ichi MatsudaAnatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Mitsuhiro KawataAnatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Earl CarstensDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, CA 95616.
Tatsuya SakamotoUshimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University, Setouchi 701-4303, Japan.
Hirotaka SakamotoUshimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University, Setouchi 701-4303, Japan.ORCID 0000-0002-6224-4591
Kyoto Prefectural University of Medicine · JPOkayama University · JPNational Institute of Genetics · JPUniversity of California, Davis · USUniversity of Toyama · JP

Funding

Role of NK-1 receptors in descending modulation and ascending transmission of itchR01AR076434 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CARSTENS, EARL E · 2020 to 2024
$1.7M
NIAMS NIH HHS R01 AR076434
6 · The paper itself

Abstract

There are sex differences in somatosensory sensitivity. Circulating estrogens appear to have a pronociceptive effect that explains why females are reported to be more sensitive to pain than males. Although itch symptoms develop during pregnancy in many women, the underlying mechanism of female-specific pruritus is unknown. Here, we demonstrate that estradiol, but not progesterone, enhances histamine-evoked scratching behavior indicative of itch in female rats. Estradiol increased the expression of the spinal itch mediator, gastrin-releasing peptide (GRP), and increased the histamine-evoked activity of itch-processing neurons that express the GRP receptor (GRPR) in the spinal dorsal horn. The enhancement of itch behavior by estradiol was suppressed by intrathecal administration of a GRPR blocker. In vivo electrophysiological analysis showed that estradiol increased the histamine-evoked firing frequency and prolonged the response of spinal GRP-sensitive neurons in female rats. On the other hand, estradiol did not affect the threshold of noxious thermal pain and decreased touch sensitivity, indicating that estradiol separately affects itch, pain, and touch modalities. Thus, estrogens selectively enhance histamine-evoked itch in females via the spinal GRP/GRPR system. This may explain why itch sensation varies with estrogen levels and provides a basis for treating itch in females by targeting GRPR.

Indexed as

AnimalsEstradiolFemaleHistamineMaleProgesteronePruritusRatsRats, WistarSex FactorsEstradiolHistamineProgesteroneestrogensgastrin-releasing peptide receptorhistamineitchspinal cord

Identifiers

PMID34312228
PMCPMC8346901
OpenAlexW3184269402

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.