Cortico-autonomic local arousals and heightened somatosensory arousability during NREM sleep of mice in neuropathic pain
- University of Lausanne, Switzerland
- Pain Center, Lausanne University Hospital (CHUV), Switzerland
- 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
Laura MJ Fernandez
Alejandro Osorio-Forero
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.
Reviewing Editor
- Rohini Kuner, Universität Heidelberg, Germany
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.
Version history
- Received: December 16, 2020
- Accepted: July 2, 2021
- Accepted Manuscript published: July 6, 2021 (version 1)
- Accepted Manuscript updated: July 8, 2021 (version 2)
- 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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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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