A zebrafish and mouse model for selective pruritus via direct activation of TRPA1
- University of Washington, United States
- Washington University in St. Louis, United States
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.
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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.
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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A zebrafish and mouse model for selective pruritus via direct activation of TRPA1
eLife 7:e32036.
https://doi.org/10.7554/eLife.32036
