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Reply to: Conceptual divide between adaptive and pathogenetic phenomena in migraine: nausea and vomiting

Peter D. Drummond, Anna Granston
DOI: http://dx.doi.org/10.1093/brain/awh280 E19 First published online: 18 October 2004

Dr Gupta raises some interesting points in relation to the interpretation of our findings (Drummond and Granston, 2004a). He notes that signs of extracranial vasoconstriction (facial pallor, constriction of conjunctival vessels) are associated with attacks of migraine, and speculates that elevations of plasma vasopressin mediate these responses. In support of this view, Gupta observes that nausea is accompanied by a spike in vasopressin release, and that levels detected during attacks of migraine are high enough to induce facial pallor. He goes on to speculate that vasopressin acts as an endogenous antimigrainous agent. This is an interesting idea that ought to be explored, but is not directly relevant to the interpretation of our results.

We found that increases in pulse amplitude (an index of blood flow) in the frontotemporal region were greater in migraine sufferers than controls during the motion sickness induced by optokinetic stimulation (Drummond and Granston, 2004a). The increase in pulse amplitude suggests that flow through dermal arterioles increases in the face during motion sickness despite an apparent reduction in flow through the cutaneous microcirculation associated with facial pallor. The greater increase in pulse amplitude in migraine sufferers than controls during motion sickness implies that the neurovascular circuit responsible for extracranial vasodilatation responds more actively in migraine sufferers than controls. This hyper-reactivity may also boost extracranial vascular responses to head pain (Drummond, 1997; Drummond and Granston, 2004b) and limb pain (Drummond and Granston, 2003), to anticipation of head pain (Drummond and Granston, 2004b), and to other forms of psychological stress (Drummond, 1982).

In cats, microinjections of an excitatory amino acid into the pretentorial part of the lateral periaqueductal grey matter induces extracranial vasodilatation in association with increases in blood pressure (Carrive and Bandler, 1991). In conscious animals, stimulation of this part of the periaqueductal grey matter evokes behavioural as well as autonomic signs of the classic defence (fight or flight) response (Bandler and Shipley, 1994). Since the defence response is provoked by threatening or stressful stimulation, we speculate that the defence response boosts extracranial vasodilatation in migraine sufferers. Dilatation of extracranial arteries is a source of pain in at least a subgroup of migrainous attacks (Drummond and Lance, 1983); thus, a hyper-reactive defence response could worsen headache.

Gupta challenges our suggestion that a deficit in normal inhibitory pain modulation persists between attacks of migraine, and claims that there is no clinical evidence of impaired (anti)nociception in migraine. This runs contrary to the notion that sensitization spreads from primary nociceptive afferents to second-order neurons in the trigeminal nucleus caudalis during attacks of migraine, and on up the neural chain to the thalamus (Burstein et al., 2000, 2004). It also overlooks substantial evidence that discomfort to a wide range of innocuous stimuli (including light and noise) peaks during attacks of migraine and persists to some extent during the headache-free interval (Drummond, 1986; Main et al., 1997; Vanagaite et al., 1997).

We postulate that a mechanism that boosts defence responses, that compromises some aspects of normal inhibitory pain modulation, and that heightens symptoms of motion sickness increases susceptibility to migraine (Drummond and Granston, 2004a). One outcome of this disturbance could be that symptoms such as nausea, photophobia and headache build upon each other in a feed-forward loop. Gupta suggests that secretion of vasopressin delays or aborts migraine attacks. The corollary, that a dip in secretion of vasopressin increases susceptibility to migraine, is one of many possibilities that deserve further study.


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