Keratinocytes can modulate and directly initiate nociceptive responses

  1. Kyle M Baumbauer
  2. Jennifer J DeBerry
  3. Peter C Adelman
  4. Richard H Miller
  5. Junichi Hachisuka
  6. Kuan Hsien Lee
  7. Sarah E Ross
  8. H Richard Koerber
  9. Brian M Davis
  10. Kathryn M Albers  Is a corresponding author
  1. University of Connecticut, United States
  2. University of Alabama, United States
  3. University of Pittsburgh, United States

Abstract

How thermal, mechanical and chemical stimuli applied to the skin are transduced into signals transmitted by peripheral neurons to the CNS is an area of intense study. Several studies indicate that transduction mechanisms are intrinsic to cutaneous neurons and that epidermal keratinocytes only modulate this transduction. Using mice expressing channelrhodopsin (ChR2) in keratinocytes we show that blue light activation of the epidermis alone can produce action potentials (APs) in multiple types of cutaneous sensory neurons including SA1, A-HTMR, CM, CH, CMC, CMH and CMHC fiber types. In loss of function studies, yellow light stimulation of keratinocytes that express halorhodopsin reduced AP generation in response to naturalistic stimuli. These findings support the idea that intrinsic sensory transduction mechanisms in epidermal keratinocytes can direct AP firing in nociceptor as well as tactile sensory afferents and suggest a significantly expanded role for the epidermis in sensory processing.

Article and author information

Author details

  1. Kyle M Baumbauer

    School of Nursing, University of Connecticut, Storrs, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jennifer J DeBerry

    Department of Anesthesiology, University of Alabama, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Peter C Adelman

    Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Richard H Miller

    Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Junichi Hachisuka

    Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Kuan Hsien Lee

    Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Sarah E Ross

    Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. H Richard Koerber

    Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Brian M Davis

    Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Kathryn M Albers

    Department of Neurobiology, Pittsburgh Center for Pain Research, Center for Neuroscience, School of Medicine, University of Pittsburgh, Pittsburgh, United States
    For correspondence
    kaa2@pitt.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Animals were handled in compliance with an approved Institutional Animal Care and Use Committee (IACUC) protocol (#14074296) of the University of Pittsburgh. All surgery was performed under appropriate anesthesia with every effort was made to minimize pain.

Reviewing Editor

  1. David D Ginty, Howard Hughes Medical Institute, Harvard Medical School, United States

Version history

  1. Received: June 25, 2015
  2. Accepted: August 28, 2015
  3. Accepted Manuscript published: September 2, 2015 (version 1)
  4. Version of Record published: September 21, 2015 (version 2)

Copyright

© 2015, Baumbauer 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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  1. Kyle M Baumbauer
  2. Jennifer J DeBerry
  3. Peter C Adelman
  4. Richard H Miller
  5. Junichi Hachisuka
  6. Kuan Hsien Lee
  7. Sarah E Ross
  8. H Richard Koerber
  9. Brian M Davis
  10. Kathryn M Albers
(2015)
Keratinocytes can modulate and directly initiate nociceptive responses
eLife 4:e09674.
https://doi.org/10.7554/eLife.09674

Share this article

https://doi.org/10.7554/eLife.09674

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