Cortico-autonomic local arousals and heightened somatosensory arousability during NREM sleep of mice in neuropathic pain

  1. Romain Cardis
  2. Sandro Lecci
  3. Laura MJ Fernandez
  4. Alejandro Osorio-Forero
  5. Paul Chu Sin Chung
  6. Stephany Fulda
  7. Isabelle Decosterd
  8. Anita Lüthi  Is a corresponding author
  1. University of Lausanne, Switzerland
  2. Pain Center, Lausanne University Hospital (CHUV), Switzerland
  3. Sleep and Epilepsy Center, Neurocenter of Southern Switzerland, Civic Hospital of Lugano, Switzerland

Abstract

Frequent nightly arousals typical for sleep disorders cause daytime fatigue and present health risks. As such arousals are often short, partial, or occur locally within the brain, reliable characterization in rodent models of sleep disorders and in human patients is challenging. We found that the EEG spectral composition of non-rapid-eye-movement sleep (NREMS) in healthy mice shows an infraslow (~50 s) interval over which microarousals appear preferentially. NREMS could hence be vulnerable to abnormal arousals on this time scale. Chronic pain is well-known to disrupt sleep. In the spared-nerve-injury (SNI) mouse model of chronic neuropathic pain, we found more numerous local cortical arousals accompanied by heart rate increases in hindlimb primary somatosensory, but not in prelimbic, cortices, although sleep macroarchitecture appeared unaltered. Closed-loop mechanovibrational stimulation further revealed higher sensory arousability. Chronic pain thus preserved conventional sleep measures but resulted in elevated spontaneous and evoked arousability. We develop a novel moment-to-moment probing of NREMS vulnerability and propose that chronic pain-induced sleep complaints arise from perturbed arousability.

Data availability

All processed data generated or analyzed during this study are included in the manuscript and supporting files. Source data files are provided for all figures. Matlab codes for major analyses are provided.

Article and author information

Author details

  1. Romain Cardis

    Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Sandro Lecci

    Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Laura MJ Fernandez

    Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7942-3369
  4. Alejandro Osorio-Forero

    Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4341-4206
  5. Paul Chu Sin Chung

    Pain Center, Lausanne University Hospital (CHUV), Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Stephany Fulda

    Sleep and Epilepsy Center, Neurocenter of Southern Switzerland, Civic Hospital of Lugano, Lugano, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Isabelle Decosterd

    Pain Center, Lausanne University Hospital (CHUV), Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  8. Anita Lüthi

    Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland
    For correspondence
    anita.luthi@unil.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4954-4143

Funding

Swiss National Science Foundation (310030_184759)

  • Anita Lüthi

Swiss National Science Foundation (310030_179169)

  • Isabelle Decosterd

Swiss National Science Foundation (320030-179194)

  • Stephany Fulda

Etat de Vaud (N/A)

  • Anita Lüthi

Etat de Vaud (N/A)

  • Isabelle Decosterd

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 experimental procedures complied with the Swiss National Institutional Guidelines on Animal Experimentation and were approved by the Swiss Cantonal Veterinary Office Committee for Animal Experimentation.

Reviewing Editor

  1. Rohini Kuner, Universität Heidelberg, Germany

Publication history

  1. Received: December 16, 2020
  2. Accepted: July 2, 2021
  3. Accepted Manuscript published: July 6, 2021 (version 1)
  4. Accepted Manuscript updated: July 8, 2021 (version 2)
  5. Version of Record published: July 20, 2021 (version 3)

Copyright

© 2021, Lüthi 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. Romain Cardis
  2. Sandro Lecci
  3. Laura MJ Fernandez
  4. Alejandro Osorio-Forero
  5. Paul Chu Sin Chung
  6. Stephany Fulda
  7. Isabelle Decosterd
  8. Anita Lüthi
(2021)
Cortico-autonomic local arousals and heightened somatosensory arousability during NREM sleep of mice in neuropathic pain
eLife 10:e65835.
https://doi.org/10.7554/eLife.65835

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