Mostly Biomathematics Lunchtime Seminar
Circadian Rhythmicity of Pain Sensitivity: A Firing-Rate Model of Dorsal Horn Circuitry
Speaker: Jennifer Crodelle, Courant Institute of Mathematical Sciences, New York University
Location: Warren Weaver Hall 1314
Date: Tuesday, February 6, 2018, 12:30 p.m.
Synopsis:
Sensitivity to painful stimuli exhibits a 24-hour circadian rhythm, with a peak during the night and a minimum in the afternoon. Patients suffering from chronic or neuropathic pain experience a phase shift in circadian rhythmicity of pain, with the peak occurring in the middle of the afternoon instead. To elucidate the mechanism underlying this phase shift, we develop a mathematical model of the neural circuitry in the dorsal horn, an area of the spinal cord that is responsible for processing nerve-fiber input and generating the resultant pain signal to the brain. We validate the model by replicating the experimentally-observed phenomenon of pain inhibition, the idea that pain can be diminished by repeated stimulation of the mechanical nerve fibers. Our model, with the inclusion of circadian effects, suggests an optimal time of day for which such stimulation provides the greatest pain relief. Finally, we use the model to investigate possible mechanisms for the observed phase shift in the circadian rhythmicity of pain that occurs under neuropathic pain conditions. Our model suggests the dysregulation of inhibition as one possible mechanistic explanation for the experimentally-observed phase shift in the circadian rhythm of pain sensitivity under neuropathic conditions.