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. 2021 Jul 2;15:705173. doi: 10.3389/fnins.2021.705173

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Copyright © 2021 Warfield, Prather and Todd.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Potential model for the travel of the pain induced positive feedback system, initiated by a neuropathic or inflammatory insult (red star), from the periphery (lower right green circle) to the spinal cord (middle green circle) and then to the brain (upper left green circle). Green arrows indicate order of activation or alteration in each system. This travel leads to altered circadian output of multiple physiological systems (where green arrows converge at bottom of top left green circle). The circadian system is also able to affect the pathway through axonal connections back from the SPZ and SCN to the LPB as well as by modulating the spinal and peripheral phenomena in chronic pain. This modulation has differing effects depending on the circadian time which is indicated by dashed green arrows.