Hi Dushyant, you are probably very aware of health problems associated with MSG added to foods.

http://www.healthline.com/health/allergies/msg#evidence2

But what is not evident is how ingested glutamate can cross the BBB and cause neurological problems.

 https://scholar.google.com/scholar?as_vis=1&q=msg+bbb&hl=en&as_sdt=1,21

Why do some people have neurological problems with ingested MSG while other people do not?

Is this a genetic trait? Is there a difference in the BBB integrity of people affected by MSG? If so, can this lead to differences in how people respond to ingested psychiatric medications? 

Just a thought. I hope this helps.

Dear Dr. Stefansson,

I really appreciate your valuable opinion. 

Though it would be interesting to investigate the mechanism of MSG triggering migraine, it may not satisfy the threshold of clinical importance that my boss has set. One can simple say that migraine sufferer should avoid any food with MSG. In other words, it's simply about allergy.

You did point out an excellent point about BBB integrity; though our technique may not have sufficient sensitivity to detect leakage of of MSG through BBB. 

Previous application of glutamate-CEST by my boss'group in epilepsy resulted in a signficant impact on clinical diagnosis itself: "Glutamate imaging (GluCEST) lateralizes epileptic foci in nonlesional temporal lobe epilepsy" 

http://stm.sciencemag.org/content/7/309/309ra161.full

Considering clinicians working on migraine at the university of Pennsylvania hospital are more convinced about cerebrovascular origin, I do need to come up with valid rationale to make them interested.

Regards,

DK

Another issue is that though there are many bio-chemical studies showing elevated glutamate in migraine, there is no conclusive evidence from imaging side (MRI, MR-spectroscopy). There could be two possible explanations-->

i) Though it could very well be the methodological fault of imaging techniique, such as lower magnetic field or sequence related. If that is the case, I would be able to do better.

ii)Other possible explanation could be that only extra-cellular glutamate may be changing. So, imaging modality, measuring total glutamate concentration (intra-cellular+ extracellular), may not be conclusive. On the other hand, biochemical testing measuring extracellular glutmate can show the role of glutamate clearly. If this is case, then there is no point in trying glutamate-CEST imaging.

Of course, I lack medical/biological background; so, I can just make guesses. 

Hi, I think I understand your predicament. Junior researchers have to carve out their own niche while not upsetting the big dogs, right?

As for MSG (glutamic acid) causing allergy doesn't make any sense what so ever. Glutamic acid is an amino acid found in every protein that we eat. The immune system does not recognize individual amino acids. If it did, we would be in big trouble because it would also recognize the closely related aspartic acid.

Anyway, again, I don't know if this will help, but C13, C14, H2 and H3 isotopes of glutamic acid and aspartic acid are probably commercially available.

Hi Dushyant:

You cannot reach Z before A. Migraine arises from the brain? You must read the following articles and the cross-references.

A further assist: Adaptive Mechanisms in Migraine. Breaking the Migraine Code. Nova Science Publications, New York, 2009.

Good Luck

Thanks Dr. Gupta, I will read through these links. I have requested book through library and hope that I will get my hand on that in a couple of days.

Please pardon me for asking; but, I did not find any mention of glutamate change being mentioned in all these three articles. 

Of course, I am interested in learning more about migraine and underlying mechanism. However, currently I am more focusing on trying to learn about the role of glutamate due to time constraint. I am trying to understand if something more can be learned from high resolution glutamate imaging of brain vs biochemical analysis.

Read up what I have recommended and I will assist you further. My pleasure, entirely. For a disease known since antiquity, time constraints??

Migraine could be due to a neurological, psychiatric or otological cause.  Personally, I think it is an peripheral vestibular disorder.  Be that as it may, whatever the primary cause I think it is likely that any brain changes are secondary to the symptoms, so reveal nothing about its primary cause.

The purpose of research is to reduce the overwhelming hedging component of "could" "should" "may" and "might". Dear Anthony, migraine is not a hopelessly complex obfuscation. The earth was flat some centuries ago, and the belief was staunchly defended. Non-believers were considered heretic. Do beta-blockers assist in peripheral vestibular disorders (pvd)? Can visual aura be explained by pvd? Do pvd start in teenage and remit in third trimester of pregnancy or after menopause? Does sleep restore any pvd? Does fasting precipitate any pvd regularly? Migraine is a protean disorder. Which pvd is protean? Which pvd rears up during menstruation? How does pvd explain lateralizing headache? Even if one patient has benefitted from PFO closure, how could that have happened with a pvd? If migraine has a neurological prodrome and  well-defined pre-prodromal phase, where does pvd fit in? I leave you with a futuristic article on migraine besides my book as mentioned above. 

NEVER FALL IN LOVE WITH YOUR OWN HYPOTHESIS--the first and last caveat for a SCIENTIST. As a human being, one "could" always be wrong.

"Can visual aura be explained by pvd"

The prevalence of peripheral vestibular disorders is higher in migraine with aura than without aura.

"Does fasting precipitate any pvd regularly?"

Fasting, weight loss or dehydration lead to reduced perilymph pressure, and resultant endolymphatic expansion (hydrops).   There is strong comorbidity (if not causal link) between hydrops, Meniere's disease and migraine.

"Do beta-blockers assist in peripheral vestibular disorders (pvd)?"

"Ménière's Disease. Symptoms of menieres disease. Info | Patient

https://patient.info/health/menieres-disease-leaflet

Ménière's disease typically causes attacks of vertigo, hearing loss, and tinnitus ... For example, thiazide diuretics or beta-blockers may help in some cases."

(I have not looked into this myself, but it did not take long to find this on Google.)

Since you have elected to respond with alacrity (as if we are in a fencing match) without much reflection on a miniscule of what was written, and you are obviously enthralled by your own hypothesis, please also let us know how nausea and vomiting of pvd (if, as it seems, migraine must be due to pvd), resolves the headache of migraine in a sizable fraction of migraineurs--a finding noted by Hippocrates but ignored by scientists of the twentieth and the twenty-first century. A pinch of salt "may" help in many medical disorders, and if Google is to replace systematic in-depth medical research and commentary, God help humanity. Like Watson and Crick, a colleague who can dampen over-enthusiasm and acknowledge error is invaluable--simply because humans find it very difficult if not impossible to acknowledge errors or limitations. Dear Anthony, let the world remain flat. I rest the case and accept your version of the "truth".

"(if, as it seems, migraine must be due to pvd)"

This study comes pretty close to showing a causal link, that migraine starts from the vestibular labyrinth:

"Vertigo as a migraine trigger

Louisa Murdin, MD,

Rosalyn A. Davies, MD, PhD and

Adolfo M. Bronstein...

doi: http:/ / dx. doi. org/ 10. 1212/ WNL. 0b013e3181b38a04 Neurology August 25, 2009 vol. 73 no. 8 638-642...

Abstract

Background: It is reported in some individual patients that vestibular stimuli can trigger migraine attacks. This study used a case-control design to examine systematically the hypothesis that vertigo induced by vestibular stimulation (rotation/caloric testing) can act as a specific migraine trigger.

Methods: A total of 123 new patients attending neuro-otology or neurology clinics were studied with questionnaires and physician interview to ascertain migraine history according to International Headache Society criteria. A total of 79 who underwent rotation/caloric vestibular testing (test group) were compared with 44 control patients in whom no such testing was carried out (control group). The principal outcome measure was the occurrence of a migraine attack within 24 hours of exposure to vestibular stimulation.

Results: Of those participants with a past history of migraines, 19/39 (49%) of the test group experienced a migraine in the study time window, compared with 1/21 (5%) of the control group. Binary logistic regression analysis confirmed that vestibular testing was associated (p < 0.05) with migraine attacks.

Conclusions: The results indicate that induced vertigo can act as a migraine trigger, a finding with implications for the diagnosis of patients with episodic vertigo and migraine headache. While such patients may well have basilar migraine or migrainous vertigo, alternatively, another disorder causing episodic vertigo (e.g., benign paroxysmal positional vertigo or Ménière disease) may be triggering migraine headaches."

"you are obviously enthralled by your own hypothesis"

If by this you mean I have carefully checked it out against possible objections, then that is true.   I now have to rely on others to point out the (fatal) flaws in my theory, and why it is not a simple, albeit unlikely, explanation for migraine.

"please also let us know how nausea and vomiting of pvd (if, as it seems, migraine must be due to pvd), resolves the headache of migraine"

   I think migraine and most (all?) nausea are triggered as reflexes from the labyrinth, as with postural or oculomotor reflexes.   There may be facilitatory or inhibitory relations between these reflexes.

   Unlike previous my assertions in this thread, this is a guess and I do not have independent evidence for this.  But does anyone proposing a cerebral origin for migraine have any better explanation for the nausea and vomiting, or why it can help?

   Alcohol has an important effect on inner ear fluids, and a drunk person can feel better after vomiting.

"please also let us know how nausea and vomiting of pvd (if, as it seems, migraine must be due to pvd), resolves the headache of migraine"

The study here strongly suggests that nausea is on the causal pathway, unlike other headache features.   Supporters of a neurological model who do not like this should instead provide any example of a well-defined neurological disease that has nausea as a component.

Headache. 2015 Jan;55(1):76-87. doi: 10.1111/head.12450. Epub 2014 Sep 24.

Persistent frequent nausea is associated with progression to chronic migraine: AMPP study results.

Reed ML1, Fanning KM, Serrano D, Buse DC, Lipton RB...

Abstract

BACKGROUND:

Though nausea is a cardinal feature of migraine, its influence on migraine progression has not been evaluated. This article aims to evaluate persistent frequent headache-related nausea (PFN) in persons with episodic migraine (EM) as a predictor of new onset chronic migraine (CM).

METHODS:

This prospective cohort study uses data from the 2007 and 2008 American Migraine Prevalence and Prevention study surveys to identify subgroups with episodic International Classification of Headache Disorders, 2nd edition defined migraine and either PFN or no or low frequency nausea (NLFN). PFN was defined by the presence of nausea ≥ half the time in both 2007 and 2008. NLFN was defined by nausea that was present