Pathophysiology of Migraine

Pathophysiology of Migraine

Educational insights developed

 
As described by Goadsby, migraine involves a
that normally modulate sensory input".
sensory modulation.

The adjacent animated image is depicting normal

afferent neural conduction from meningeal vasculature. 
These neurons of the first division of the trigeminal
nerve are "reporting" the status of the vessels to the
trigeminal sensory nucleus.  The status may be that
there has been enlargement of the arteries due to the
presence of nitric oxide (as described below), or of a
degree of inflammation.  This is not a state of pathology
and is the normal responsibility of the first order sensory
neurons.

The pathophysiology of migraine is a condition of

abnormal responses to normal sensory inputs.  Current
therapeutic modalities for migraine simply stipulate this
fact, and embark on altering the nature of
neurotransmitter activity, either preceding the event
(preventive medications), or during the event (abortive
or "rescue" drugs).

What has been generally overlooked is the etiology* of

the abnormality of the sensory modulation.  *(how it got
that way and/or how it stays that way)

While the current medical models for migraine

from the meningeal arteries to the trigeminal s
  acute or chronic noxious afferent input from th
primarily the mandibular (third) division and ho
sensory modulation, has been essentially igno
General background
Medical research has identified two
consistent features present in chronic
migraine patients: an elevated
sympathetic tone , and, in those patients
with "aura" preceding the attack, a wave
of cortical depression (as pictured to the
right).

The susceptibility to this depression is

either a genetic property of the subject,
or is an environmental
adaptation/alteration of normal.
 
The depression is actually a "switching
off" and then switching back on of the
brain cells as the area of the wave
passes. This wave of depression
typically initiates in the occipital area of
vision.  The visual aura (sometimes
described as concentric areas of
blindness) that is sometimes reported
occurs simultaneously with the
depression in that area.

As the brain cells "switch back on", nitric oxide (NO) is produc
brain.  There, the NO causes the surface arteries to swell [left
trigeminal nerve fibers that wrap around these arteries.
     It is not uncommon for a person to experience this wave o
being triggered.  Sometimes, instead of an aura (a result of th
in the occipital region), some people experience other physica
tingling/numbness, or feeling a bit "spacey" for short periods.
As the swelling enlargement of the
intracranial surface arteries  stimulates
sensory fibers of V1 (ophthalmic branch
of the trigeminal, V), "noxious" (meaning
potentially harmful) information is
relayed to (afferent) the sensory nucleus
of the trigeminal. 

Then, either as a result of genetic

properties of the host (as in a pre-
existing elevated sympathetic tone), or
as a result of a pre-sensitization of the
sensory nucleus (addressed further
below), or both, Calcitonin Gene-Related
Peptide (CGRP) is secreted by the
nerve endings of V1 (as are other
noxious chem-
icals), thereby producing a frank
inflammation of the arteries, which is
thought to be primarily responsible for
the patient's pain, throbbing and
aversion to movement.
Perhaps in an attempt to counter-act the
elevated sympathetic tone that occurs in
response to the rapidly inflamed arteries,
acetylcholine (ACh) is secreted by the
parasympathetic nerve endings from the
sphenopalatine ganglion (SPG), thereby
causing swelling, pressure and
inflammation of the nasal mucosa and
also causes a heightened tension of the
intrafusal fibers of the spindles primarily
within the temporalis muscle (the main
muscle of jaw clenching, a result of
chronic elevated sympathetic tone),
creating the sensation of tension or
squeezing.  The intense pain from
spasming of these intrafusal fibers
("migraineous pain")  far exceeds that of
the chronic spindle tension of tension-
type headache.

Sensitized neurons from the trigeminal spinal track cause infl

 
occipital nerve and artery, causing cervical tension and pain.
Most of the arterial concepts of migraine have been focused on the enlargement of intracranial surface
exposure to nitric oxide.  However, the effect of the release of peptides such as CGRP on the extracra
corresponding trigeminal nerve branches has been largely overlooked and considerably under-rated.
The three most commonly reported  locations of pain and "pressure" are the:  nasal sinuses (left);
The sinuses are highly vascularized, while the temporal and occipital regions includes major arterial tre
and each are adversely effected the by release of neural peptides.
The "pre-sensitization" of the Trigeminal Sensory Nucleus
The animation [right] depicts normal
masticatory motor and sensory activity
(chewing).  Of the three branches of the
trigeminal nerve, the third division (the
mandibular, or V3) is the largest and
most active, due mainly to the
abundance of sensory input from the
oral cavity and temporomandibular joint.

During a normal chewing stroke, the

motor nucleus of V innervates the
elevating (closing) musculature of the
mandible.  As forces escalate on the oral
structures, proprioceptive and
nocioceptive afferent input to the
mesencephalic and sensory ganglia
serve to govern the forces applied.
At a certain threshold, elevating innervation is discon
depressor (opening) activity ensues.

An elevated sympathetic tone increases EXCESSIVE NOXIOUS AFFEREN

the intrafusal tension of the spindles
(primarily within the temporalis) and
allows nocturnal jaw-elevator muscle
activity to go un-governed, resulting in
multiple nightly episodes of jaw-
clenching activity that can exceed the
subject's voluntary maximum. [right]. 
While casually referred to as "bruxism",
the term has unfortunately become
synonymous with  "teeth-grinding". 
Although teeth-grinding can ensue as a
result of the persisting jaw elevation and
occluding of the teeth, the intensity of
the elevator muscle activity (primarily the
temporalis), dictates whether or not the
jaw depressors/openers (mainly the
lateral pterygoids) can success-
fully advance their respective condyles,
resulting in varying degrees of teeth-
grinding.

An elevated sympathetic tone increases the intrafusal tension

temporalis) and allows nocturnal jaw-elevator muscle activity
nightly episodes of jaw-clenching activity that can exceed the
While casually referred to as "bruxism", the term has unfortun
 
grinding".  Although teeth-grinding can ensue as a result of th
of the teeth, the intensity of the elevator muscle activity (prima
not the jaw depressors/openers (mainly the lateral pterygoids
respective condyles, resulting in varying degrees of teeth-grin
Less-than-maximal clenching activity in
the presence of a "malocclusion" (an
occluding scheme of the teeth that
obligates protective activity of the lateral
pterygoid in order to protect the jaw-joint
and mal-positioned teeth during
chewing) can elicit considerable noxious
afferent stimulation of the sensory
nucleus, thereby further adding to its
sensitization. 
The sensitized nucleus becomes
"triggerable", responding to otherwise
harmless noxious stimulations (i.e.,
glare, odors, food additives), and
anything that further naturally elevates
sympathetic tone.

In the absence of moderate to intense nocturnal clenching, de

  "adjustments" of the teeth, orthodontics, mouth splints, and cr
noxious masticatory and nocturnal parafunctional stimulation.
While the frequency and duration of INHIBITION OF NOXIOUS SENSORY ACTI
parafunctional episodes remain a (resulting in reduction of migraine attacks)
function of the host's sympathetic tone,
the intensity of the acts and position of
the condyles can be influenced by a
strategically designed oral orthotic.*

     In order to achieve excessive

contraction intensities of the elevating
musculature, the posterior and/or canine
teeth must first occlude with each other,
thereby "completing the circuit" and
providing the resistance necessary to
allow intense contraction activity (as in
the animation above).

     By limiting the dental occluding

contacts to include incisor teeth only
(excluding the canine teeth) in any
lateral movement of the mandible by the
lateral pterygoids, the elevator muscle
contraction is inhibited to <30% of
voluntary maximum.

By limiting the degree of separation of the posterior and canin

particular alterations of the orthotic), the translation of the con
can also be minimized or eliminated.
 
*The NTI device (Nociceptive Trigeminal Inhibition), approved
medically diagnosed migraine pain and Temporomandibular D
82% of migraine patients reported a 77% average reduction o
weeks of use.  Duration and intensity of migraine attacks wer
The charts to the right are recordings of LONG TERM EFFICACY
temporalis EMGs (clenching intensities) ( 6-year use follow-up survey:
of a migraine sufferer between midnight
and 3am for 13 consecutive nights. 
Each vertical spike is a clenching
episode.

The patient had been wearing an NTI

device for over two years, with complete
resolution of her daily headaches and
frequent migraine attacks. 

Nights 1 through 5 show her still using

her NTI.  The circled purple number 
represents the level of headache pain
upon waking (on a scale of 0-10 with 10
being worst pain imaginable).  She was
restless and disturbed by the EMG leads
for the first three nights.  By the fifth
night, she had become accustomed to
them. 

Nights 6 through 9 are without using her

NTI.  She had been offered $50 per
night (for up to 10 consecutive nights), to
go without her NTI.