|
Summary: It is generally accepted that migraine is caused by a
primary biochemical disorder of the central nervous
system involving neurotransmitters, specifically
serotonin. The pathogenetic mechanism triggered by
external and internal stimuli is not well explained or
understood. This article points to the possibility
that the pineal gland, a primary source of central
serotonin and melatonin, contributes significantly to
migraine attacks. © 2001 Harcourt Publishers Ltd.
INTRODUCTION
The
current theory defines migraine as a primary
neurogenic rather than primary vascular dysfunction,
caused by excessive external and internal stimuli
which reach thethalamus, hypothalamus and cerebral
cortex, a dysfunction characterized by abnormal
serotonin metabolism, and overactive trigeminovascular
system. Such a dysfunction leads to transient
neuralgic symptoms and signs and to vasodilatation and
inflammation of craniocerebral blood vessels and
headaches. Other neurotransmitters have been
implicated including nor epinephrine and endorphins.
No mention has been made, as far as I know, of the
role played by melatonin, which is a producer of the
pineal serotonin, except in my 1986 publication (I).
Migraine
begins with hypothalamic symptoms two or three days
prior to the headache, including changes in mood,
appetite and thirst, the so-called ‘prodrome
phase.’ When the trigeminovascular system becomes
more active, on account of loss or diminished
inhibition by the serotonergic center in the brainstem
(Raphe Nuclei), the headache begins with nausea,
vomiting and photophobia. About 10—20 minutes prior
to the headache, the patient
may
develop a variety of transient neurological symptoms
or signs. These are caused by depolarization of
cerebral neurons. These may be confined to the
occipital visual cortex in which case the migraine is
classified as ‘classic.’
When
other areas are involved, the migraine is classified
as ‘complicated’ (I see no logical reason to
separate these two types of migraine).
The
most significant diagnostic finding is the fact that
migraine is frequently triggered by a variety of
external and internal factors such as certain foods,
perfumes, flickering lights, loss of sleep, traveling
through time zones, hypoglycemia, menses etc. Another
diagnostic finding is that migraine may be prevented
by anticonvulsants and aborted by Ergot preparations
and serotonin agonists, called triptans, but not as
much by analgesics and even opioids.
Even
though the current theory is generally accepted, it
does not explain why or how external triggers disrupt
the normal metabolism of the intracerebral serotonin.
Considering that most of the intracerebral serotonin
is produced in the pineal gland, and that the pineal
gland is a link between the environment and the CNS,
particularly light, I continue to raise the questions
of the relation between the hypothalamus (for internal
stimuli), the pineal gland (for external stimuli) and
the action of serotonin (and melatonin) on the CNS
(2).
Some
anatomists (2) question the release of pineal products
directly into the CSF because there is no definite
evidence of anatomical communication between the
pineal gland and the cerebral ventricles. Others have
melatonin and migraine demonstrated, however, that
such communication is physiologically present; in
fact, a fluorescent dye introduced in the cerebral
ventricle completely penetrates the parenchyma of the
pineal gland, at least in cats (3). If such a
communication exists, it is logical to assume that
both serotonin and melatonin could influence the
cerebral neurons of the hypothalamus, thalamus,
brainstem and cerebral cortex.
THE
ACTION OF SEROTONIN AND MELATONIN
The
influence of serotonin and melatonin on the activity
of the CNS has been widely investigated by pineal
researchers (3—18). Serotonin is the product of
dietary tryptophan. About 900/o of serotonin is
produced in the walls of the gastrointestinal tract,
stored in platelets and distributed to the rest of the
body, except the CNS, because serotonin does not cross
the blood—brain barrier.
When
tryptophan, which crosses the blood—brain barrier,
reaches the CNS, it is converted into cerebral
serotonin. The circulating tryptophan will also reach
the pineal gland where it is converted into serotonin;
this conversion occurs during daylight with the
assistance of beta-receptors in the pinealocytes. At
night, the pineal serotonin is converted by a special
enzyme (HIMOT) into melatonin.
Pineal
serotonin released in the CSF increases the activity
of cerebral neurons but decreases the activity of the
serotonergic neurons (4) of the Raphe Nuclei, which
normally inhibit the trigeminovascular system. When
this inhibition is controlled, the hyperactivity of
the trigeminovascular system leads to dilation and
inflammation of cerebral vessels in the domain of the
trigeminal nerve headache)!
The
influence of melatonin has been also widely
investigated, particularly with relation to the
metabolism of serotonin, the activity of cerebral
neurons and the endocrine system. Whereas serotonin
released by the pineal gland in the CSF leads to
decreased activity of the serotonergic Raphe Nuclei,
melatonin does just the opposite (4). Therefore less
melatonin also leads to decreased
activity of the Raphe Nuclei. The combination
of excessive serotonin and diminished melatonin leads
to increased trigeminovascular activity which is
responsible for the headache phase of migraine.
THE
HYPOTHESIS
Intraperitoneal
injection of melatonin in cats will at first increase
the anticonvulsant activity of the neurotransmitter
gamma amino butyric acid and deplete the serotonin in
the cerebral cortex by 500/i within 20 minutes,
whereas
180
minutes later the serotonin in the Raphe Nuclei is
still elevated. One may postulate that melatonin would
be effective in relieving the neurological findings
seen early in complicated migraine and the Raphe
Nuclei will control
the
trigeminovascular system as late as 9 hours after the
injection of melatonin!
|
