Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors

Abstract

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated MrgprdCreERT2 mouse line. We found that mouse plantar paw skin also innervated by a low density of Mrgprd+ nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the 'enlarged representation' of plantar paw regions in the CNS.

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Author details

  1. William Olson

    Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ishmail Abdus-Saboor

    Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Lian Cui

    Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Justin Burdge

    Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Tobias Raabe

    Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Minghong Ma

    Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Wenqin Luo

    Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    For correspondence
    luow@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2486-807X

Funding

National Institute of Neurological Disorders and Stroke (NS083702)

  • Wenqin Luo

Burroughs Wellcome Fund (PDEP)

  • Ishmail Abdus-Saboor

National Institute of Neurological Disorders and Stroke (NS094224)

  • Wenqin Luo

National Institute of Neurological Disorders and Stroke (NS092297)

  • William Olson

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

Ethics

Animal experimentation: All procedures were conducted according to an animal protocol (#804886) approved by Institutional Animal Care and Use Committee (IACUC) of the University of Pennsylvania and National Institutes of Health guidelines.

Copyright

© 2017, Olson 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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https://doi.org/10.7554/eLife.29507

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