TY - JOUR

T1 - Provoked versus spontaneous migraine attacks

T2 - pathophysiological similarities and differences

AU - Ashina, Håkan

AU - Christensen, Rune Häckert

AU - Ashina, Messoud

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - Background: The onset and duration of spontaneous migraine attacks are most often difficult to predict which, in turn, makes it challenging to study the neurobiologic underpinnings of the disease in a controlled experimental setting. To address this challenge, human provocation studies can be used to identify signaling molecules (e.g. calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide) that, upon intravenous or oral administration, induce migraine attacks in people with migraine and mild or no headache in healthy volunteers. This approach has proven to be valid for decades and plays an integral role in mapping signaling pathways underlying migraine pathogenesis and identification of novel drug targets. However, the question arises as to whether the pathogenic mechanisms of provoked and spontaneous migraine attacks differ. In this paper, we provide an opinionated discussion on the similarities and differences between provoked and spontaneous attacks based on the current understanding of migraine pathogenesis. Methods: The PubMed database was searched in July 2022 for original research articles on human provocation studies that included participants with migraine. The reference lists of originally identified articles were also searched and we selected those we judged relevant. Discussion: People with migraine describe that provoked attacks resemble their spontaneous attacks and can be treated with their usual rescue medication. From a neurobiologic standpoint, provoked and spontaneous migraine attacks appear to be similar, except for the source of migraine-inducing substances (exogenous vs. endogenous source). In addition, provoked attacks can likely not be used to study the events that precede the release of migraine-inducing signaling molecules from sensory afferents and/or parasympathetic efferents during spontaneous attacks.

AB - Background: The onset and duration of spontaneous migraine attacks are most often difficult to predict which, in turn, makes it challenging to study the neurobiologic underpinnings of the disease in a controlled experimental setting. To address this challenge, human provocation studies can be used to identify signaling molecules (e.g. calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide) that, upon intravenous or oral administration, induce migraine attacks in people with migraine and mild or no headache in healthy volunteers. This approach has proven to be valid for decades and plays an integral role in mapping signaling pathways underlying migraine pathogenesis and identification of novel drug targets. However, the question arises as to whether the pathogenic mechanisms of provoked and spontaneous migraine attacks differ. In this paper, we provide an opinionated discussion on the similarities and differences between provoked and spontaneous attacks based on the current understanding of migraine pathogenesis. Methods: The PubMed database was searched in July 2022 for original research articles on human provocation studies that included participants with migraine. The reference lists of originally identified articles were also searched and we selected those we judged relevant. Discussion: People with migraine describe that provoked attacks resemble their spontaneous attacks and can be treated with their usual rescue medication. From a neurobiologic standpoint, provoked and spontaneous migraine attacks appear to be similar, except for the source of migraine-inducing substances (exogenous vs. endogenous source). In addition, provoked attacks can likely not be used to study the events that precede the release of migraine-inducing signaling molecules from sensory afferents and/or parasympathetic efferents during spontaneous attacks.

KW - Aura

KW - Headache

KW - Premonitory Symptoms

KW - Trigeminovascular System

KW - Trigger Factors

U2 - 10.1186/s10194-022-01464-2

DO - 10.1186/s10194-022-01464-2

M3 - Review

C2 - 35870898

AN - SCOPUS:85134652793

VL - 23

JO - Journal of Headache and Pain

JF - Journal of Headache and Pain

SN - 1129-2369

IS - 1

M1 - 87

ER -