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.
Bès A et
al Hypersensibilité dopaminergique
dans la migraine: un test diagnostique ?
La Nouvelle Presse
Médicale1982; 11; 19
Heinrichs
L Linking olfaction with nausea and
vomiting of pregnancy, recurrent abortion,
hyperemesis gravidarum, and migraine headache
Headache 2003; 43; 3;
304-5
Jacome D
Compulsive yawning as migraine premonitory
symptom Cephalalgia 2001 Jun;
21; 5; 623-5
James
MF,Smith J M et al Cortical spreading
depression and migraine: new insights from
imaging? Trends in Neurosciences
May 2001; vol 24; n 5; p 266-271
Loder
A What
is the evolutionary advantage of migraine ?
Cephalalgia 2002; 22;
624-632
Peres
MF et al Hypothalamic involvement in chronic
migraine J Neurol Neurosurg
Psychiatry 2001; 71; 747-751
Sabatini U
et al Migraine attacks induced by
subcutaneous apomorphine in two migrainous
parkinsonian patients Clinical
Neuropharmacology1990; 13; 3;
264-267
Szechtman
H et al Sensitization and Tolerance to
Apomorphine in Men: Yawning, Growth Hormone,
Nausea, and Hyperthermia
Psychiatry Research 1988, 23,
245-255
