Hippocampal oscillatory dynamics and sleep atonia are altered in an animal model of fibromyalgia: Implications in the search for biomarkers

J Comp Neurol. 2020 Jun;528(8):1367-1391. doi: 10.1002/cne.24829. Epub 2019 Dec 14.

Abstract

The pathogenesis of fibromyalgia is still unknown. Core symptoms include pain, depression, and sleep disturbances with high comorbidity, suggesting alterations in the monoaminergic system as a common origin of this disease. The reserpine-induced myalgia (RIM) model lowers pain thresholds and produces depressive-like symptoms. The present work aims to evaluate temporal dynamics in the oscillatory profiles and motor activity during sleep in this model and to evaluate if the model mimics the sleep disorders that occur in fibromyalgia patients. Hippocampal and electromyogram activity were recorded in chronically implanted rats. Following 3 days of basal recordings, reserpine was administered on three consecutive days to achieve the RIM. Postreserpine recordings were taken on alternate days for 21 days. Reserpine induced changes in the sleep architecture with more transitions between states, and a different pattern between the administration period and postreserpine weeks. Administration days were characterized by a larger amount of rapid eyes movement sleep with dominant theta waves without atonia. Following the reserpinization, theta oscillations were always more fragmented and with lower frequency. On the postreserpine days, sleep was dominated by slow-wave sleep with fast intrusions and reduced hierarchical coupling with spindles and ripples. Simultaneous electromyography recordings also showed muscle twitches during sleep and the dissociation of theta activity and muscle atonia. Abnormally high slow waves, alpha/delta intrusions, frequent transitions, and muscle twitches are common traits in fibromyalgia. Therefore, our analyses support the validity of the RIM model to study sleep disorders in fibromyalgia, and provide new insights into the research of oscillographic biomarkers.

Keywords: (RRID:SCR_000432); MATLAB (RRID:SCR_001622); RStudio; chronic pain; fibromyalgia; hippocampus; reserpine; sleep.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / toxicity
  • Brain Waves / drug effects
  • Brain Waves / physiology*
  • Electroencephalography / drug effects
  • Electroencephalography / methods
  • Fibromyalgia / chemically induced
  • Fibromyalgia / physiopathology*
  • Hippocampus / drug effects
  • Hippocampus / physiopathology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reserpine / toxicity*
  • Sleep / drug effects
  • Sleep / physiology
  • Sleep Wake Disorders / chemically induced
  • Sleep Wake Disorders / physiopathology*

Substances

  • Antipsychotic Agents
  • Reserpine