Propranolol came into migraine research by pure accident or simplistic chance or retrogressive serendipity in 1967, leaving science and the migraine research community to struggle for its pharmacological mode of action in migraine. Propranolol also made a major dent or detour in theoretical considerations and therapies for migraine, driving neurologists away from reason and logic in the understanding of migraine.
Science is not free of fashion. Propranolol is the old-fashioned lady left far behind in the vogue of research, but the secret of migraine is hidden carefully in the folds of her clutch handbag (it could well also be the almost-ancient gentleman clutching his wallet, carrying the prized possession with somewhat wanton malice) that generations of scientists / migraine researchers have sought with desperation laced with nihilism. However, when migraine researchers call themselves 'scientists', a high wall (and loud wail) of beliefs and myths immediately stands up to question the honour.
Since tertiary-care / Institutional researchers and august Headache Conferences around the world are not seized with the matter over 50 years later, busy as they are with CGRP and other neuropeptides, let us join together and explore our collective wisdom and insight or even speculation.
Or shall we leave this scientific resolution to the next millennium?
I assure the fraternity of migraine researchers that no meaningful progress will be made unless this conundrum, the Rubik Cube of migraine, is resolved
I set the ball rolling with 4 of my published articles.
Come, join me.
ORCID: hrttps://orcid.org/0000-0002-6770-5916
Propranolol as a beta-blocker drug , sometimes it can be prescribed for the prevention of migraines. Propranolol act by preventing vasodilation and stabilizing serotonin levels. If patient benefits propranolol well, therefore migraine attacks will be shorter in duration, less intense, and less frequent.
Do all beta-blockers prevent migraine? Why are beta-blockers only partially effective in preventing migraine?
To try to answer its route of action, perhaps it is wise to revisit the understanding of the underlying pathophysiology. Till recently the model revolved around the trigemino-vascular model. Fine as it goes but it is only an intermediate step!
For me migraines are an abnormal response to a normal process. The brain is of course electrical. Go to a cell level and one can explore multiple membrane ion chanels, but essentially these result in varied neuronal excitability excitability levels in groups of neurones, and ultimately the entire brain
Without excitability you're dead and too much you will potentially have a continuous epileptic seizure. Obviously on a group level the neurones have positive and negative feedback loops, often with interneurones. Look at the pyramidal cells in the cortex, a building block that is repeated billions of times. On top of this we have opposing general network control systems mediated by the sympathetic and parasympathetic systems. The latest kid on the block is how a dysbiotic gut biome can end up by increasing afferent sympathetic messaging through 'leaky gut syndrome'
The analogy of migraine setting off a fire alarm (headache) is not new. The fire alarm is a necessary function but if it is too sensitive then this is not good! We can translate this to a more scientific and informative description of Network Neuronal Hyperexcitability
So as a starting point it is hardly surprising that 'calming' drugs such as propranolol, amitriptyline, candesartan etc can all potentially reduce ion channel activity and reduce neuronal excitability with variable efficacy
We also know that hormone pathways, particularly estrogens, are important
My interest is vagus nerve stimulation as a route to reducing hyperexcitability on a network level. In particular there is the Daith Ear piercing to give a continuous low grade stimulation of the Auricular Branch of the Vagus by irritation rather than electrical. It can work extremely well and is very inexpensive, and could be distributed to poor nations who have no money for the simple drugs let alone CGRP blockers that can cost $5000 a year
The history and details of the research over the last 7 years (including the latest 2023 paper) can be seen at www.migraine-research.org/useful links
- Badges
- Science topic
- Similar topics
- Biological Science
- Molecular Cell Biology
- Culture Cells
- Cell Line