This most important issue has been swept-under-the-carpet of the massive and exponentially increasing data bank of migraine. Stress is a very common trigger for migraine, and, post-stress migraine attacks are the commonest form of migraine.
No extant theory of migraine rationalizes stress/post-stress migraine attacks-- neuronal, neurovascular, vascular, neuroinflammation, neuropeptides from serotonin to CGRP/VIP/PACAP/Prostaglandins, oxidative stress, brain involvement from cerebral to cerebellar to thalamic to hypothalamic to brainstem, central to peripheral sensitization with allodynia, ANS involvement from sympathetic to parasympathetic dysfunction from pupillary changes to catecholamines to cardiac autonomic dysfunction, systemic blood pressure changes, meningeal involvement, primary sensory dysfunction, primary brain neuronal hyperactivation including cortical spreading depression / spreading depression, biobehavioural model, alcohol imbition or its withdrawal (morning 'hangover' headaches), sleep studies, cocaine exposure and abstinence, experimental glyceryl trinitrate challenge, dietary/allergic exposures, gut-brain axis, brain magnesium depletion, animal experimental evidences, and much more.
There is no central hypothesis to place the massive and exponentially ever-increasing data of migraine in a robust generalizable logically-defensible and biologically plausible matrix.
Nearing the end of my self-motivated independent unsponsored research career in migraine with 6 decades of ceaselessly working towards such a unifying theory for migraine, and, living with migraine, I want to share my insight with my peers, current and future. Knowledge of stress/post-stress related migraine mechanisms and the adaptation of the human body to stressors will pave the way for the future. All theory and therapy in migraine / primary headache is empirical, including patent foramen ovale closure. [Gupta, Exp Rev Neurother, 2010]
A massive change in scientific perception is required. I completed this task in 2009 in my book: "Adaptive Mechanisms in Migraine. A Comprehensive Synthesis in Evolution. Breaking the Migraine Code". Nova Science, New York, 2009.
Future generations of scientists need to work towards a basic understanding of migraine and not hide it in mountains of data, and, know where to start to cut through the assumptions and myths that have drowned migraine research in despair and nihilism. Data and mathematical and default theories of the past 7 decades have robbed us of our critical thinking. The mysteries around propranolol and amitritptyline and much more will unfold following this lead.
The key lies in understanding of stress/post-stress mechanisms. There is a fundamental difference between Institutional support and the quest for the search. Research grants can create data, not the truth. Imagination is the key to the unending quest for unveiling the mysteries of Nature. Data rob you of the humility to approach the research question, as Medawar [1967, The Art of the Soluble. Metheun, London) also emphasized. All data are selective, piecemeal, divisive, making one see the trees for the wood.
Like Blau, Welch, and Lance encouraged me in 1997, I encourage the future of migraine research with these historic personal communications. An open mind, free of preconception - a sine qua non. Archimedes and Newton are examples of the capability of the free untethered unfettered mind.
Let us study stress / post-stress mechanisms, and, evolve the science of primary headaches/migraine further with an impetus never before generated. The study will guide you into the future of the discipline.
ORCID ID:https://orcid.org/0000-0002/6770/5916
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