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Investigating Circadian Rhythmicity in Pain Sensitivity Using a Neural Circuit Model for Spinal Cord Processing of Pain

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Women in Mathematical Biology

Part of the book series: Association for Women in Mathematics Series ((AWMS,volume 8))

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Abstract

Primary processing of painful stimulation occurs in the dorsal horn of the spinal cord. In this article, we introduce mathematical models of the neural circuitry in the dorsal horn responsible for processing nerve fiber inputs from noxious stimulation of peripheral tissues and generating the resultant pain signal. The differential equation models describe the average firing rates of excitatory and inhibitory interneuron populations, as well as the wide dynamic range (WDR) neurons whose output correlates with the pain signal. The temporal profile of inputs on the different afferent nerve fibers that signal noxious and innocuous stimulation and the excitability properties of the included neuronal populations are constrained by experimental results. We consider models for the spinal cord circuit in isolation and when top-down inputs from higher brain areas that modulate pain processing are included. We validate the models by replicating experimentally observed phenomena of A fiber inhibition of pain and wind-up. We then use the models to investigate mechanisms for the observed phase shift in circadian rhythmicity of pain that occurs with neuropathic pain conditions. Our results suggest that changes in neuropathic pain rhythmicity can occur through dysregulation of inhibition within the dorsal horn circuit.

The original version of this chapter was revised. An erratum to this chapter can be found at https://doi.org/10.1007/978-3-319-60304-9_13

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Acknowledgements

This work was conducted as a part of A Research Collaboration Workshop for Women in Mathematical Biology at the National Institute for Mathematical and Biological Synthesis, sponsored by the National Science Foundation through NSF Award DBI-1300426, with additional support from the University of Tennessee, Knoxville. This work was additionally partially supported by the following sources: NSF Award DMS-1412119 (VB) and the Pritzker Neuropsychiatric Disorders Research Consortium (MH). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

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Authors and Affiliations

  1. Department of Mathematical Sciences, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA

    Jennifer A. Crodelle

  2. Department of Applied Mathematics and Computer Science, Technical University of Denmark, 2800, Kongens Lyngby, Denmark

    Sofia H. Piltz

  3. Department of Mathematics, University of Michigan, Ann Arbor, MI, 48109, USA

    Victoria Booth

  4. Department of Anesthesiology, University of Michigan, Ann Arbor, MI, 48109, USA

    Victoria Booth

  5. Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, 48109, USA

    Megan Hastings Hagenauer

Authors
  1. Jennifer A. Crodelle
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  2. Sofia H. Piltz
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  3. Victoria Booth
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  4. Megan Hastings Hagenauer
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Correspondence to Victoria Booth .

Editor information

Editors and Affiliations

  1. Department of Mathematics, Duke University, Durham, North Carolina, USA

    Anita T. Layton

  2. Departments of Mathematics and Biology, University of North Carolina, Chapel Hill, North Carolina, USA

    Laura A. Miller

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Crodelle, J.A., Piltz, S.H., Booth, V., Hagenauer, M.H. (2017). Investigating Circadian Rhythmicity in Pain Sensitivity Using a Neural Circuit Model for Spinal Cord Processing of Pain. In: Layton, A., Miller, L. (eds) Women in Mathematical Biology. Association for Women in Mathematics Series, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-319-60304-9_2

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