- To most researchers, as has often seemed the case in medical literature --- the term biological stands for "laboratory, or genetic, or non-environmental or physiological or organic " -- modified from van Pragg et al., Handbook of Biological Psychiatry, Marcel Dekker. Inc. New York / Basel, 1979.
- Laboratory medicine is intrinsically reductionist, the exclusive focus on one or two factors giving the entity a false identity. Now, migraine is far from being a disorder that might be almost fully explained by aberrations in serotonin or any of the neuro-peptides that are well-known or that keep emerging on the horizon. As Blau said so eloquently decades ago, neuropeptides are like Hospital Administrators -- they really do no work !!
- So, what is the biology of MIGRAINE?
- HAS THE TERM "BIOLOGICAL" been MISPLACED OR MISUNDERSTOOD, deliberately or by accident, IN MIGRAINE RESEARCH?
- Straight Quote from my book: ADAPTIVE MECHANISMS IN MIGRAINE. A COMPREHENSIVE SYNTHESIS IN EVOLUTION. BREAKING THE MIGRAINE CODE. NOVA SCIENCE PUBLISHERS, INC., NEW YORK, 2009:
- "THE BIOLOGY OF AN ILLNESS IS THE ELUCIDATION OF THE FORCES THAT PUSH AN INDIVIDUAL TOWARDS THE DISEASE OR THE DISEASE-FREE STATE. THE FIRST STEP IN THE EVOLUTION OF A BIOLOGICALLY-DRIVEN OVERARCHING THEORY FOR MIGRAINE IS THE ELUCIDATION OF THE PHYSIOLOGICAL FORCES (PROCESSES) THAT PUSH OR PULL THE PATIENT TOWARDS THE AURA-HEADACHE OR THE AURA-HEADACHE FREE STATE, SIGNIFICANTLY DELAY ONSET OF THE MIGRAINE ATTACK (WITH OR WITHOUT AURA) FOR SEVERAL HOURS TO A FEW DAYS AFTER EXPOSURE TO DIVERSE ATTACK-PROVOKING STIMULI, ALLOW PATIENTS TO FUNCTION DESPITE THE ATTACK-RELATED MORBIDITY, KEEP PATIENTS IN EXTENDED (BUT VARIABLE) REMISSIONS, AND PREVENT ATTACKS IN FOUR-FIFTHS OF THE GENERAL POPULATION" (Gupta VK. 2004. Stress, adaptation, and traumatic -event headaches: pathophysiologic and pharmacotherapeutic insights. BMC Neurology, 26 November 2004). (see attached file below).
- I regard the above-paragraph as the single most important statement / sentence to propel MIGRAINE research forward to its logical conclusion.
- I put this up on ResearchGate as a insight-bestowing philosophical gift for all members, whether or not involved in migraine research, whether belonging to the current or future generations of any era, whether appreciative or critical of my fledgling efforts to see through the many veils of NATURE & SCIENCE, whether regarding my sincere efforts to understand MIGRAINE as ethical jingoism or egoism or as a form of anxiety or self-aggrandizement or self-interest or self-promotion, as the primary tool to understand the occult mystery of medical sciences.
- Nature always seeks the prepared mind (Carlo Rubbia, CERN). Scientific discovery is originally based on intuition or imagination, and is much closer to the creative process of the artist than readers of scientific papers realize. (A. Storr, Lancet 1993; 341 (April 24): 1062-1063).
- Since you have seen the dust, see the WIND.
- Since you have seen the foam, see the Ocean.
- Come see it, for insight is the only thing in you that avails;
- the rest of you is piece of fat and flesh. (Jalaluddin Rumi, Poet and mystic. Selections from his writings. (translated by RA Nicholson). London: Allen and Unwin, 1950).
- Securing a publication in SCIENCE is certainly not the same as having a peep into TRUTH. Science without such philosophic mooring at this depth is a recipe for near-permanent wanderings in the lovely woods of knowledge from the bench or the bedside or both.
- In effect, I give you -- current and future generations of scientists in medical or in the other fields of human scientific endeavour -- the key to the mysterious occult of the science of medical and other researches.
Stress, adaptation, and traumatic-event headaches: pathophysiologic and pharmacotherapeutic insights. BMC Neurology.
26 November 2004
- Vinod Gupta, Dubai Police Medical Services, Dubai, United Arab Emirates
- Haas suggests mental alteration as a possible aetiology for post-traumatic headaches [1]. To discusss mental alteration(s) or psychogenic headache as an underlying pathogenetic factor [1] without mentioning stress is surprising. On the other hand, the term “stress” is frequently misused to hide gaps in our comprehension of complex medical situations [2]. If bodily injuries might be discounted as the cause of the headaches [1], the peri- and post-injury stress along with the pre-injury trait or constitutional factor(s) hold the key to the evolution of the pathophysiology of post-traumatic headaches.
- A key clinical clue to the nature of post-traumatic chronic headaches is the variable onset of the symptoms, ranging from minutes to a few (upto 7 days) [1]. A similar delay in onset of headache is seen in migraine, with headache developing after a significant period of (i) stress, exercise, or ingestion of alcohol [3]; (ii) ingestion of tyramine containing foods, involving a delay upto 22 hours [4]; cocaine abuse or abstinence [5,6]; caffeine withdrawal over the weekend [7]; exposure to m-chlorophenylpiperazine (m-CPP) [8]; and nitroglycerine ingestion or infusion [9]. Primary headache associated with catastrophic psychological (non-physical) trauma is similarly associated with a significant delay in onset [10].
- The physiological system(s) primarily affected in migraine and post-traumatic headache must necessarily be afforded a considerable (but limited and exhaustible) degree of protection by homeostatic defense mechanisms, thereby allowing the subject to continue to function despite the stressful stimulus or situation; this protection is obviously unlimited or inexhaustible in the majority of the general population who are not susceptible. “Good medicine is indivisible, has always been holistic in the sense that it considered the whole patient, has always seen the patient balanced between opposing forces pushing him towards health or disease…the ability to continue to function in the period immediately after acute injury....and the variations in the effects of the same injury in the same individual from time to time just as between individuals is unlikely to be unifactorial or a 'hopelessly complex' obfuscation, but is probably the result of a meticulously orchestrated parallel activation of multiple physiological (secondary stress or adaptive) processes” [11]. The clinical circumstances discussed above as well as the variable prodrome of migraine that lasts for several hours or a few days [12] after exposure to the potentially noxious stimulus or situation is analogous to the period after an "acute injury" during which the migraine subject remains largely unaware of the threat of impending painful cephalic disturbance and continues to function appropriately. The variable period between the physical injury to any part of the body and onset of headache is similarly a time interval during which adaptive physiological processes operate efficiently to keep the headache at bay.
- The literature of migraine, though inexhaustible, contains hardly any reference to the possibility of operation of natural adaptive responses that promote or preserve vascular integrity (including calibre), pain control (antinociception), behavior adaptation, and overall functional capacity in the setting of a variety of stressful stimuli and situations that herald impending painful cephalic disturbance. In general, stress and or pain release AVP [13] and it is certainly not difficult to imagine how diuresis can interfere with the mounting of an effective adaptive response and maintain functional capability during any form of stress (fight, flight or fright) including, for instance, a boxing match, an interview, an examination, or more specifically the interval preceding the migraine attack or following trauma. A neuroendocrine adaptive “system” that maintains vascular integrity, antinociception, and behaviour during migrainous vasodilatory antidromic trigeminal nerve discharge has been recently proposed [14]. Such an adaptive-protective “system” is secondarily activated following exposure to the headache-provoking stimulus -- stress or trauma, including trauma to the head or whiplash injury -- and delays the onset of migrainous or non-migrainous headache. Such an adaptive reaction is essentially limited and liable to fatigue variably in different patients as well as in the same patient on different occasions; onset of headache (acute attack or chronic) possibly represents overwhelming or fatigue of this adaptive “system”. The components of this adaptive mechanism include sympathetic nervous system activation coupled to enhanced bioavailability of serotonin and vasopressin. The relevance of alterations of vasopressin bioavailability -- both increase or decrease -- to migraine pathophysiology has been discussed previously [14]. The precise source of the antidromic trigeminal nerve discharge that precipitates the headache is a matter of speculation as yet, but there are serious reservations for considering a central brain / brain stem origin for migraine [15]. Trait factors are probably more important in predisposing to headache following trauma than minor structural alterations in the head-neck axis.
- Amitriptyline is a possibly a drug of choice in the management of post-traumatic headaches. Maximally tolerated doses should be tried before therapeutic failure with amitriptyline is accepted. As reviewed, tricyclic antidepressants increase vasopressin release from the neurohypophysis [14]. Contrary to the general belief in primary headache research, amitriptyline is not a central brain serotonergic antagonist [16]. Also, insofar as brain noradrenergic function is concerned, the combination of amitriptyline and propranolol is pharmacologically paradoxical, as amitriptyline unambiguously activates brain noradrenergic function. Nevertheless, this combination works in some patients, the basis of which remains unknown.
References
1. Haas DC. Traumatic-event headaches. BMC Neurology 2004, 4:17.
2. Gupta VK. Sympathetic nervous system dysfunction in migraine: pearls and pitfalls in the theorizing process. Headache 2004, 44:841-842.
3. Blau, JN. Migraine: theories of pathogenesis. Lance 1992, 339, 1202--1207.
4. Poole, CJM. Migraine. Br J Hosp Med 1986, 36: 90-93.
5. Satel SL, Gawin FH. Migrainelike headache and cocaine use. JAMA 1989, 261: 2995--2996.
6. Dhuna A, Pascaul-Leone A, Belgrade M. Cocaine-related vascular headaches. J Neurol Neurosurg Psychiatry 1991, 54: 803--806.
7. Couturier EGM, Hering R, Steiner TJ. Weekend attacks in migraine patients: caused by caffeine withdrawal? Cephalalgia 1992, 12:99--100.
8. Brewerton TD, Murphy DL, Mueller EA, Jimerson DC. Induction of migraine-like headaches by the serotonin agonist m-chlorophenylpiperazine. Clin Pharmacol Ther 1988, 43:605-609.
9. Thomsen LL, Kruuse C, Iversen HK, Olesen J. A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks. Eur J Neurol 1994, 1:73-80.
10. Shulman BH. Psychiatric aspects of headache. Med Clin North Am 1991, 75:707-715.
11. Wall PD, Melzack R. Textbook of Pain, 2nd ed. New York: Churchill Livingstone, 1989.
12. Peatfield R. Drugs and the treatment of migraine. Trends Pharmacol Sci 1988, 9:141-145.
13. Valiquette G. The neurohypophysis. Neurol Clin 1987, 5: 291--331.
14. Gupta VK. A clinical review of the adaptive role of vasopressin in migraine. Cephalalgia 1997, 17:561-569.
15. Gupta VK. Migraine following haemorrhage in brain stem cavernous angioma: pathophysiological considerations. J Neurol Neurosurg Psychiatry 2003 [Published online on 23 June 2003]. Available at: http://jnnp.bmjjournals.com/cgi/eletters/74/5/680#55.
16. Gupta VK. Amitriptyline versus cyproheptadine: opposite influences on brain 5-HT function. Headache 2005 (In press).
Competing interests
None declared
Last paragraph of my book under Epilogue, page 73 (Adaptive Mechanisms in Migraine-A comprehensive synthesis in Evolution. Breaking the Migraine Code, Nova Science Publishers, Inc., 2009" (straight quotation):
"Where the primary intuition come from, however, is pure mystery, and perhaps, fittingly so. The intellectual strength of science lies in its essentially subversive character (Horton, 1995; 346:3). The origin of inspired scientific intuition lies in the obscure subversive mental processes that refuse to accept compromises in knowledge that have passed as science for centuries or millennia. A simple, Timeless Awareness (Aldous Huxley, The Perennial Philosophy, Triad Grafton Books, London, 1985) or the Timeless Original Mind (A. Watts. The Way of Zen, New York, Vintage, 1989) determines the final telluric instrument of unburdening, etching in temporal terms the push from the past and the pull from the future. In science and art, life's mega-illusion of being the doer is amplified manifold for the instrument. "It is not we who possess art; rather, it is art...that sometimes takes possession of people and in part manifests itself through them"-- Andrei Donatovivh Sinyavsky.
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