The Modulation of Pain by Circadian and Sleep-Dependent Processes: A Review of the Experimental Evidence

Megan Hagenauer, Jennifer Crodelle, Sofia Helena Piltz, Natalia Toporikova, Paige Ferguson, Victoria Booth

Research output: Chapter in Book/Report/Conference proceedingArticle in proceedingsResearchpeer-review


This proceedings paper is the first in a series of three papers developing mathematical models for the complex relationship between pain and the sleep–wake cycle. Here, we briefly review what is known about the relationship between pain and the sleep–wake cycle in humans and laboratory rodents in an effort to identify constraints for the models. While it is well accepted that sleep behavior is regulated by a daily (circadian) timekeeping system and homeostatic sleep drive, the joint modulation of these two primary biological processes on pain sensitivity has not been considered. Under experimental conditions, pain sensitivity varies across the 24 h day, with highest sensitivity occurring during the evening in humans. Pain sensitivity is also modulated by sleep behavior, with pain sensitivity increasing in response to the build-up of homeostatic sleep pressure following sleep deprivation or sleep disruption. To explore the interaction between these two biological processes using modeling, we first compare the magnitude of their effects across a variety of experimental pain studies in humans. To do this comparison, we normalize the results from experimental pain studies relative to the range of physiologically meaningful stimulation levels. Following this normalization, we find that the estimated impact of the daily rhythm and of sleep deprivation on experimental pain measurements is surprisingly consistent across different pain modalities. We also review evidence documenting the impact of circadian rhythms and sleep deprivation on the neural circuitry in the spinal cord underlying pain sensation. The characterization of sleep-dependent and circadian influences on pain sensitivity in this review paper is used to develop and constrain the mathematical models introduced in the two companion articles.
Original languageEnglish
Title of host publicationWomen in Mathematics
Number of pages21
Publication date2017
ISBN (Print)9783319603049
Publication statusPublished - 2017
EventResearch Collaboration Workshop for Women in Mathematical Biology - NIMBioS, University of Tennessee, Knoxville, Knoxville, United States
Duration: 22 Jun 201525 Jun 2015


WorkshopResearch Collaboration Workshop for Women in Mathematical Biology
LocationNIMBioS, University of Tennessee, Knoxville
CountryUnited States
SeriesWomen in Mathematical Biology


  • Mathematics
  • Physiological, Cellular and Medical Topics
  • Mathematical Modeling and Industrial Mathematics

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