Human tissue studies in primary headache disorders: A scoping review

Abstract

Background: Despite the identification of structures with putative pathophysiological significance in primary
headache disorders (e.g., posterior hypothalamus in cluster headache) there appears to be a paucity of
human tissue studies examining the neuropathology of these regions.
Objective: To synthesize the extent and knowledge pertaining to direct human tissue analysis in primary
headache disorders.
Methods: Scoping literature review.
Results: Of 2718 located articles, 15 were eligible for inclusion. These studies evaluated either migraine (9,
60%) or cluster headache (6, 40%). Approximately 75% were published before or during the era of the first
edition of the International Classification of Headache Disorders. The most common study design was
case-control (8, 53.3%), and the most commonly examined tissues equally included skin (3, 20%), muscle (3,
20%), and brain (3, 20%). Thematically, these manuscripts generally evaluated peripheral nervous and
systemic pathology, as well as more targeted pathophysiological aspects, including mitochondrial and
mast cell dysfunction.
Conclusions: While interest in this type of study design appears to be waning, histopathological evaluation
of human tissue provides unparalleled opportunity to reveal novel pathophysiological insight. Considerations
for future study design and reporting of work involving human tissue is suggested based on our review.