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A zebrafish and mouse model for selective pruritus via direct activation of TRPA1

  1. Kali Esancy
  2. Logan Condon
  3. Jing Feng
  4. Corinna Kimball
  5. Andrew Curtright
  6. Ajay Dhaka  Is a corresponding author
  1. University of Washington, United States
  2. Washington University in St. Louis, United States
Research Article
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Cite this article as: eLife 2018;7:e32036 doi: 10.7554/eLife.32036

Abstract

Little is known about the capacity of lower vertebrates to experience itch. A screen of itch-inducing compounds (pruritogens) in zebrafish larvae yielded a single pruritogen, the TLR7 agonist imiquimod, that elicited a somatosensory neuron response. Imiquimod induced itch-like behaviors in zebrafish distinct from those induced by the noxious TRPA1 agonist, allyl isothiocyanate. In the zebrafish, imiquimod-evoked somatosensory neuronal responses and behaviors were entirely dependent upon TRPA1, while in the mouse TRPA1 was required for the direct activation of somatosensory neurons and partially responsible for behaviors elicited by this pruritogen. Imiquimod was found to be a direct but weak TRPA1 agonist that activated a subset of TRPA1 expressing neurons. Imiquimod-responsive TRPA1 expressing neurons were significantly more sensitive to noxious stimuli than other TRPA1 expressing neurons. Together, these results suggest a model for selective itch via activation of a specialized subpopulation of somatosensory neurons with a heightened sensitivity to noxious stimuli.

Data availability

The following previously published data sets were used

Article and author information

Author details

  1. Kali Esancy

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Logan Condon

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jing Feng

    Center for the Study of Itch, Washington University in St. Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Corinna Kimball

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrew Curtright

    Department of Biological Structure, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ajay Dhaka

    Department of Biological Structure, University of Washington, Seattle, United States
    For correspondence
    dhaka@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5783-8582

Funding

National Institutes of Health (R01DE23730)

  • Ajay Dhaka

Mary Gates (Undergraduate Research Research Award)

  • Logan Condon

Levinson Emerging Scholars Award (Undergraduate Research Award)

  • Logan Condon

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments using zebrafish were performed under the University of Washington Institutional Animal Care and Use Committee protocols #4216-02 (approved on 9/16/2016). The University of Washington Institutional Animal Care and Use Committee (IACUC) follow the guidelines of the Office of Laboratory Animal Welfare and set its policies according to The Guide for the Care and Use of Laboratory Animals. The University of Washington maintains full accreditation from the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) and has letters of assurance on file with OLAW. The IACUC routinely evaluates the University of Washington animal facilities and programs to assure compliance with federal, state, local, and institution laws, regulations, and policies. The OLAW Assurance number is DL16-00292.

Reviewing Editor

  1. Allan Basbaum, University of California, San Francisco, United States

Publication history

  1. Received: September 15, 2017
  2. Accepted: March 19, 2018
  3. Accepted Manuscript published: March 21, 2018 (version 1)
  4. Version of Record published: April 23, 2018 (version 2)

Copyright

© 2018, Esancy et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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