mise à jour du
13 mars 2003
1994; 34(9); 536-538
Video assessment of yawning induced by sublingual apomorphine in migraine
Del Bene E, Poggioni M, De Tommasi F
Institute of Internal Medicine and Therapy, Headache Centre
University of Florence, Italy


Introduction : During a migraine attack, pain is usually accompanied by a few clinical signs such as nausea, vomiting, shivering, and sometimes circulatory collapse and hallucinations which have been postulated to be due to a central dopaminergic dysfunction. Yawning may precede or accompany pain during a migraine attack. This behavioral sign is mainly controlled by the dopaminergic system; also the cholinergic and endocrine systems (ACTH, oxytocin, MSH, and androgens) seem to play a role. Some investigations have demonstrated that migraine sufferers show a hyperresponsiveness to pharmacological dopaminergic stimulation.

Apomorphine, a dopamine receptor agonist, has been shown to induce yawning in healthy volunteers. A previous study carried out in our laboratories has shown that 100 µg of sublingual apomorphine may induce headache, nausea, vomiting, drowsiness, and yawning in migraine sufferers. It has also been observed that migrainous women with Parkinson's disease treated with apomorphine show typical migraine crises accompanied by the above described characteristic clinical signs.

Pharmacologically-induced yawning may be used to reveal possible central dopaminergic latent dysfunctions in migraine sufferers during interictal periods. A preliminary open study suggested that apomorphine-induced yawning is significantly increased in migraine patients. In the present double-blind, placebo-controlled study, the measurement of yawning induced by sublingual apomorphine in migraine sufferers was carried out by using an audiovisual technique.

Discussion : Yawning is a common behavioral manifestation both in animals and man; its mechanism and physiological role are poorly understood.

Numerous studies indicate that dopaminergic pathways are involved in the intricate physiological mechanism underlying yawning. Ferrari and Gessa found that the administration of the corticotrophic hormone (ACTH) and of the melanophor hormone (alpha-MSH) into the cerebrospinal fluid induces yawning and stretching in experimental animals. Further studies in animals have proved that even dopaminomimetic drugs and oxytocin provoke yawning and penile erection. It seems that apomorphine induces yawning by releasing oxytocin at the level of the hypothalamic paraventricular nucleus. Apomorphine seems to induce yawning by interacting with D2 dopaminic receptors: a stimulation of Dl postsynaptic dopamine receptors cannot be excluded, as also D1's antagonists seem to block yawning induced by D2 agonists

Yawning and other psychic and physical signs (nausea, vomiting, feeling cold, hypotensive crises) which often accompany or precede migraine are thought ta be caused by dopaminergic activation. Small doses of dopaminomimetic drugs induce an intense hypotensive response in migraineurs, the venoconstrictive action of dopamine is more intense in migraine sufferers than in controls and low doses of apomorphine and L-dopa induce a hyperemetic response in headache sufferers but not in controls. Piribedil infusion increases central blood flow and causes nausea, vomiting, and hypotension. This test has been used to assess dopaminergic sensitivity in migraine. An open study has shown that subcutaneous apomorphine provokes an enhanced yawning response in migraineurs in comparison to controls.

The present study shows that sublingual administration of apomorphine can induce yawning in migraine sufferers with a higher frequency than in controls. Apomorphine was administered in microdoses (about 1/100 of the dose used in Parkinson's disease ) because of the known hyperresponsiveness of migraine patients to dopaminomimetics. The results confirm the hypothesis of a dopaminic hypersensibility in migraine sufferers.

The audiovisual technique used in the present study appears to be a simple, harmless, repeatable objective method to evaluate behavioral phenomena both in basal conditions and after pharmacological manipulations. In conclusion, the video assessment of apomorphine-induced yawnng represents a useful tool to study the central dopaminergic systems involved in the pathogenesis of migraine.

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