Why Pain Feels Worse at Night & Disrupts Sleep?

Pain syndromes encompass not only physical and sensory symptoms but also involve emotional and cognitive alterations such as functional impairment, negative affect, feelings of stress, and fatigue. In rodents, chronic inflammatory pain induced by intraplantar injection of Complete Freund's Adjuvant (CFA) leads to anhedonia and disruptions in natural behaviors, similar to uncontrolled stress responses.

Building on this understanding, on June 22, 2025, William A. Carlezon Jr.'s research team at McLean Hospital, USA, published a study in the journal Neuropsychopharmacology titled "Inflammatory pain in mice induces light cycle-dependent effects on sleep architecture." This research reveals that inflammatory pain in mice triggers changes in sleep architecture that are dependent on the light cycle.

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Overview

The authors investigated whether these similarities also extended to changes in sleep and rhythm, mirroring those induced by chronic social defeat stress. They observed mice using both actigraphy and wireless electroencephalography (EEG). The experiment compared differences between groups of mice that received injections at the beginning of either the light or dark cycle.

The authors discovered that CFA-induced inflammatory pain altered the sleep architecture in both male and female mice. Most notably, during the dark phase (when mice are typically more awake), total sleep time increased, accompanied by longer sleep bouts and shorter wake bouts. Conversely, during the light phase, sleep bouts shortened, indicating more fragmented sleep. Similarly, CFA-induced increases in the duration and number of Rapid Eye Movement (REM) sleep and Slow-Wave Sleep (SWS) predominantly occurred during the dark phase. These dark-phase effects were highly consistent in mice injected either at the beginning of the dark cycle or 12 hours prior, whereas the light-phase effects were more dependent on the time elapsed since injection. Furthermore, the injection also led to non-specific alterations in circadian rhythmicity.

The authors' findings suggest that inflammatory pain significantly increases sleep during the normally active phase and impacts the transitions between sleep and wakefulness throughout the entire day.

Findings of the Study

In summary, the authors found that inflammatory pain significantly increased sleep during the normally active phase and altered the transitions between sleep and wakefulness throughout the entire day. This research not only elucidates the complex effects of inflammatory pain on sleep architecture but also highlights the crucial role of circadian rhythms in this process. It provides an important animal model and mechanistic clues for studying the interaction between pain and sleep, while also laying the groundwork for future clinical translation and the optimization of therapeutic strategies.

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Reference

1. Burek, Dominika J et al. "Inflammatory pain in mice induces light cycle-dependent effects on sleep architecture." bioRxiv : the preprint server for biology 2024.08.28.610124. 29 Aug. 2024, doi:10.1101/2024.08.28.610124. Preprint. Distributed under Open Access license CC BY 4.0, without modification.