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Papers of the Week

2021 Apr 01




Migraine Triggers: An Overview of the Pharmacology, Biochemistry, Atmospherics, and Their Effects on Neural Networks.


We define a migraine trigger to be an endogenous agent or agency such as the menses or an exogenous agent or agency such as red wine or a drop in barometric pressure, and their ability to reduce the threshold of a migraine attack in those predisposed to migraine. This definition excludes agents with idiosyncratic mechanisms that may trigger a migrainous (migraine-like) headache in non-migraineurs such as benign cough headaches or headaches due to altitude-sickness. We also assume as axiomatic that migraine has as its basis the activation of the trigeminovascular pathway (TVP) and the key role of serotonin and the calcitonin gene-related peptide (CGRP). The network activation of the visual/auditory association cortices and the rostrodorsal pons (locus ceruleus and raphe nucleus) are also accepted as key features of activation of the TVP. In addition, we outline the role of the superior salivatory nucleus-sphenopalatine ganglion-greater superficial petrosal nerve (SSN-SPG-GSPN) arc in migraine activation. We also explore how olfactory afferents intermingle with trigeminal nerve collaterals in the glomeruli of the olfactory bulb thus allowing volatile molecules to activate the TVP and induce a migraine. The classification of migraine triggers is complex, as there is a wide panorama of inciting agents, including atmospheric conditions, a wide-ranging variety of foods and beverages, endogenous hormonal influences, synthetic alkaloids and dyes, and volatile molecules (odorants). We will explore the high-frequency migraine-provoking agents in each category. There are exciting and intriguing hypotheses regarding the role of atmospheric chemistry when the barometric pressure drops; the role of hot, dry desert winds and lightning discharges in the generation of cations and the turnover of serotonin in the nervous system. We will explore the effects of a drop in barometric pressure on the vestibular nuclei and the modulation of sympathetically mediated pain. The role of volatile odorants and their activation of the transient receptor potential ankyrin-1 (TRPA-1) receptor will be outlined. We will streamline the highly complex role of estrogen fluctuation in the precipitation of migraine headaches, its pharmacodynamic effects, and the role of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of the hypothalamus. We will also adumbrate the protean effects of alcohol and its congeners and the role of stress and sleep disturbances in the allostatic load model of salience network-pain perception.