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Curr Pain Headache Rep. 2019 Jul 29;23(9):62. doi: 10.1007/s11916-019-0799-4.

Linking Traumatic Brain Injury, Sleep Disruption and Post-Traumatic Headache: a Potential Role for Glymphatic Pathway Dysfunction.

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Department of Pediatrics, Division of Child Neurology, Doernbecher Children's Hospital, Oregon Health & Science University, 707 SW Gaines St. CDRC-P, Portland, OR, 97239, USA.
Department of Neurology, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
Oregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR, USA.
VA Portland Health Care System, Portland, OR, USA.
Center for Policy and Research in Emergency Medicine, Department of Emergency Medicine, Oregon Health & Science University, Portland, OR, USA.
Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd. L459, Portland, OR, 97239, USA.
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.



Traumatic brain injury (TBI) is a major public health concern in the USA and worldwide. Sleep disruption and headaches are two of the most common problems reported by patients after TBI. In this manuscript, we review the current knowledge regarding the relation between post-traumatic sleep disruption and headaches. We also describe the role of the glymphatic system as a potential link between TBI, sleep, and headaches.


Recent studies show a reciprocal relation between post-traumatic sleep disruption and headaches: patients with sleep disruption after TBI report more headaches, and post-traumatic headaches are a risk factor for developing disrupted sleep. Despite this clinical association, the exact mechanisms linking post-traumatic sleep disruption and headaches are not well understood. The glymphatic pathway, a newly described brain-wide network of perivascular spaces that supports the clearance of interstitial solutes and wastes from the brain, is active primarily during sleep, and becomes dysfunctional after TBI. We propose a model where changes in glymphatic function caused by TBI and post-traumatic sleep disruption may impair the clearance of neuropeptides involved in the pathogenesis of post-traumatic headaches, such as CGRP. The relation between TBI, post-traumatic sleep disruption, and post-traumatic headaches, although well documented in the literature, remains poorly understood. Dysfunction of the glymphatic system caused by TBI offers a novel and exiting explanation to this clinically observed phenomenon. The proposed model, although theoretical, could provide important mechanistic insights to the TBI-sleep-headache association.


Concussion; Glymphatic system; Headaches; Sleep; Traumatic brain injury


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