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  1. Stress, adaptation, and traumatic-event headaches: pathophysiologic and pharmacotherapeutic insights

    Vinod Gupta, Dubai Police Medical Services, Dubai, United Arab Emirates

    26 November 2004

    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.


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    Competing interests

    None declared