Theory

Introduction

A Migraine is a neurological disorder that manifests most commonly as headache attacks lasting 4–72 hours. Migraine headaches most commonly appear as a severe throbbing pain or a pulsing sensation, usually on one side of the head, associated with various combinations of neurologic, gastrointestinal, and autonomic symptoms.^[1]

Gastrointestinal symptoms normally include: nausea, vomiting, abdominal cramps, or diarrhea. Neurologic  symptoms manifest as photophobia (Sensitivity to light), phonophobia (Sensitivity to sound), and osmophobia (Sensitivity to smells) as well as cognitive dysfunctions, an inability to concentrate & communicate, irritation and more. Finally, autonomic symptoms can include blurry vision, nasal stuffiness, tenesmus, polyuria, pallor, sweating, temperature intolerance, and others.^[2]

Migraine is most often associated with its accompanying headache, however there are multiple types of migraine, some of which, such as abdominal migraine, may even manifest without a headache.^[3],[4] Migraine can be considered episodic, if it manifests for 14 days a month or less, or chronic, if it manifest for 15 or more days a month^[5].

Migraine is usually managed by medication, but the currently available oral pharmacological migraine treatments may be poorly tolerated by some patients. Unpleasant side effects and lower than hoped for efficacy^[6]. 

The use of non-pharmacological treatments for migraine represents an expanding clinical practice and interesting area of research, these may include invasive or non invasive stimulation of various cranial nerves which have been found to be effective^[7] . At the same time various randomized clinical trials suggest that non technological methods such massage therapy, physiotherapy, relaxation and chiropractic spinal manipulative therapy might be equally effective as propranolol and topiramate in the prophylactic management of migraine, while others suggest that they have no significant effect^[8]. In parallel, behavioral interventions for migraine such as relaxation training, stress management, cognitive-behavioral therapy, ACT and biofeedback have been shown to be effective in diminishing migraine frequency^[9],[10].

Migraine types and manifestation

Migraine is divided to two main types:

1. Migraine without aura is characterized by headache coupled with the neurologic and physiological symptoms described before.
2. Migraine with aura is primarily characterized by transient neurological symptoms that usually precede or sometimes accompany the headache, usually in the form of a visual disturbance known as a scintillating scotoma.^[11]

A typical migraine attack manifests in 4 stages:

1. Prodrome

The prodrome, starting upto 48 hours a migraine episode reaches its peak intensity, is characterized by premonitory symptoms of an impending migraine. Prodrome symptoms may include: Thirst or Food cravings, Constipation or diarrhea, Nausea, Muscle stiffness or soreness, especially in the neck, Fatigue or Excessive yawning, Increased frequency of urination, Difficulty concentrating, Mood changes: sadness, irritability, anxiety, Sensitivity to light, sounds, or smells & Feeling cold.^[12],[13]

2. Aura

About 1 in 3 people with migraines experience an “aura” that begins before the headache or starts along with it^[14]. An aura is a set of transient, reversible neurological symptoms that may include: Changes in vision, such as a flickering, jagged arc of light that slowly expands towards the edges of the visual field over several minutes, known as a scintillating scotoma.^[15] This manifestation can be accompanied by a blind spot in the field of vision, and an inability to recognize objects, or hallucinate images.^[16]

Migraine aura can also manifest “weird” skin sensations. Such as tingling or numbness, starting in the face and hands and spreading out to the rest of the body.^[17] Or even cognitive and communicative abnormalities including: a difficulty expressing thoughts in writing or speech, confusion, difficulty concentrating or understanding.^[18]

Migraine aura last from 20min to 2hours, and is usually followed by the attack phase^[19].

3. Attack Phase

The attack phase of a migraine can last from a few hours to several days. Migraine headaches usually begin above the eyes, and affect one side of the head; but may shift from one side to another, or engulf the entire head. It may also affect the lower face and the neck. The pain tends to feel throbbing, and tends to worsen with physical activity and leaning forward^[20].

During the attack phase additional symptoms such as unusual and extreme sensitivity to light, sounds, and smells causing pain can appear. And vestibular symptoms, such as lightheadedness and fainting, as well as Nausea and vomiting are prevalent.^[21]

4. Postdrome

Following the attack, a period of time known as the postdrome lasting on average 18-25 hours follows. During this time tiredness, concentration difficulty, and neck stiffness are the most typically reported postdrome symptoms.^[22]

Migraine Diagnosis

In order to diagnose migraine, separate from other headaches the following conditions must be met:

Patient must complain of at least 5 headache attacks that lasted 4–72 hours (untreated or unsuccessfully treated) and the headache must have had at least 2 of the following characteristics:

• Unilateral location
• Pulsating quality
• Moderate or severe pain intensity
• Aggravation by or causing avoidance of routine physical activity (eg, walking, climbing stairs)

In addition, during the headache the patient must have had at least 1 of the following:

• Nausea and/or vomiting
• Photophobia (light sensitivity) and phonophobia (sound sensitivity)

Finally, these features must not be attributable to another disorder. Normally a CT scan and blood tests will be applied in order to rule out other causes.^[23]

What causes migraine?

The Pulsating nature of some migraine headaches, led in the 19th and 20th centuries to the formation of a ‘Vascular theory of migraine’. According to this theory the dilation of extracranial arteries causes a mechanical activation of stretch receptors innervating the arteries, resulting in throbbing headache pain.^[24] However clinical studies failed to show that this arterial dilation could produce headaches,^[25] and that the pulsations during a migraine attack are not synchronized with cardiac contractions, leading to this theory being abandoned.

Today migraine is more commonly described as a “neurovascular disorder” that involves meningeal blood vessels, the pain fibers that innervate them, which are part of the Trigeminal nerve, and structures of the CNS that become hypersensitized due to this activation. This hypersensitization involves three levels of neurons.

1. First order trigeminovascular neurons, the peripheral nerves that innervate the intracranial vasculature and the meninges, originate from the trigeminal ganglion, innervating the face, the head and the meninges, these neurons project into structures in the pons.
2. Second order neurons located in the principal sensory nucleus of trigeminal nerve in the medullary dorsal horn. At this level (SpV, TCC, TCN) located in the brain stem there is an intersection with nerve fibers that innervate the neck, and the vagus nerve. The neurons at this level receive these signals, interprets them and passes them on to the thalamus.
3. Third order neurons in the thalamus, connect to various other sensory input from the body, and are affected by modulatory neurons coming from the prefrontal cortex (PFC) and the Anterior Cingulate Cortex (ACC). and connect the second order trigeminovascular neurons to the primary sensory cortex, where pain is finally perceived to be localized. These nerves play a part in the secondary symptoms of migraine such as photophobia, phonophobia and complete body allodynia.^[26],[27]

The Process of sensitization

In migraine these structures become sensitized, lowering their signaling threshold and creating a condition by which they are relentlessly sending nociceptive signaling (pain signals) to the cortex, due to any kind of stimulation, such as light touch, blood flow etc.

It is believed that the sensitization process in migraine begins with a neuroinflammation of these structures^[28], experiments in mice have shown that by creating an inflammation in the meninges by using noxious chemicals triggers this sensitization process.^[29] This neuroinflammation is spontaneous migraine is believed to be the result of Cortical spreading depression (CSD), the most probable cause of the migraine aura, and a similar but symptomless process in migraine without aura. ^[30]

CSD is a wave of electrophysiological hyperactivity followed by a wave of inhibition in neuronal activity^[31], creating a change in neuronal metabolism and therefore demand on blood flow is the cause of both the Migraine Aura^[32]. In its wake a soup of inflammatory peptides are released which cause the nerves innervating the meninges to become sensitized^[33]. They in turn cause the second order nerves in the SpV to become sensitized and they, the third order neurons in the thalamus^[34].

How Manual Neuromodulation Migraine & Headache therapy (MNMHT) works?

MNMHT involves the application of the following main elements:

• Manual manipulations, that take the form of mainly pressure or massage of various locations innervated by branches of the Trigeminal nerve
• Deep abdominal breathing
• Progressive muscular relaxation
• And mindful non reactive awareness of pain.

In addition secondary elements relating to prophylactic treatment may be applied:

• Spinal manipulation
• Abdominal massage
• Forced left nostril breathing

During an MNMHT session the patient is asked to perform one or more of approx 30 physical manipulations, involving pressure points, neck stretches, and massage, to various areas, mainly in the head and back. At the same time as they are applying these manipulations the patients are instructed to perform deep abdominal breathings, facial gestures, and relax muscular tension in the face and body. Patients are also instructed to maintain a non-reactive mindful state of mind as they perform these techniques. The techniques are performed in specific sequences which prescribed based on the patients’ specific headache phenotype, and are each propounded to connect to specific migraine symptoms including the pain location, quality of pain, and symptoms like nausea, irritation and cognitive dysfunctions..

During the application of the procedures patients normally report a transient increase of their pain index, with increase in pain referral and manifestation of various tactile and vestibular sensations such as expansion, dizziness, ‘openness’, a procession of pain along certain pathways in the head and more.

This increase is followed by a rapid and often sudden cessation of migraine symptoms including pain, nausea, photophobia and cognitive disabilities, in some cases while the pain ceases immediately, cognitive disabilities and fatigue continue to ensue, both of which are relieved within 30-90 minutes of resting, or with the application of forced left nostril breathing.

The cessation of migraine symptoms is often accompanied with an emotional release, eructation, and parasympathetic phenomenology such as lacrimation, stuffy nose, yawning, and sighing.

Manual manipulations

One of the most effective cutting edge migraine relief technologies are wearable electronic devices, that emit electrical signals to various parts of the Trigeminal nerve, this signaling creates a pain gating phenomena that has been found to be helpful for many migraine patient.

The physical manipulations of MNMHT  are designed to elicit the same kind of effect as these electronic neruomodulation devices, but with physical exercises. The manipulations are applied based on the headache phenotype, and specifically the location of pain reported by the patient.

During the application of the manipulation, first order pain relaying nerve endings of Aδ fibers (fast firing), and C fibers (slow firing) of the trigeminal ganglion, innervating extracranial structures are stimulated.^[35] In addition it is possible that dural pain relaying fibers that traverse the calvarial connecting the intracranial pia and extracranial periosteum are stimulated as well^[36].

Applied in the beginning stages of a migraine, when these first order neurons are in the process of sensitization is the speculated cause for the perceived increase in headache intensity by the patients during the application of the techniques. This pain is probably mediated via fast the acting Aδ fibers.

Pain gating may be partly responsible for the relief in pain seen in the application of MNMHT. Trigeminal Aβ fibers, stimulated by the massage/pressure, and converging with C-fibers &  Aδ fibers at the level of the spinal trigeminal nucleus caudalis may be involved in producing this gating effect. But it might also be possible that the Aδ fibers themselves directly are also responsible for pain gating. This would explain the relative increase in acute pain, transmitted by these nerve fibers which is experienced during the performance of the techniques, and the subsequent diminish in throbbing pain transmitted via C fibers that is experienced once the manipulation is halted.^[37]

Progressive muscular relaxation

The second integral part of MNMHT is a continuous progressive muscular relaxation designed to elicit the relaxation response in patients. The relaxation response, defined by Benson as being opposite to the fight or flight stress response^[38], includes decreased oxygen consumption and carbon dioxide elimination, lowered heart rate, arterial blood pressure, and respiratory rate. The relaxation response appears to be an integrated hypothalamic response resulting in generalized decreased sympathetic nervous system activity.^[39] Pain perception has been shown to create unconscious musculoskeletal contractions^[40], and it is suggested that the opposite muscular relaxation prevents the sensitivity developed against the pain. The analgesic effects of the relaxation response is attributed to the hypothalamic pituitary adrenal axis (HPA) and the sympathoadrenal medullary (SAM) system.

Deep Abdominal breathing

The third integral part of MNMHT is deep abdominal breathing. Deep rhythmic breathings have been shown to increase vagal tone^[41], especially when emphasis is put on elongating exhalations. Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS), a method for activating the Vagus nerve through its pulmonary branch has shown to have therapeutically significant pain modulation effects. ^[42].

Electrical invasive and non-invasive Vagus Nerve Stimulation (VNS) is another neuromodulation technique employed today for the relief of migraines. First created with the purpose of preventing epileptic seizures it has been found to have a very strong potential in relieving migraine as well.

VNS has a downregulating effect on migraine pain via the inhibitory connection between the vagus nerve to the second order Trigeminal pain relaying neurons in the TCC and TCN

Deep rhythmic breathings have been shown to stimulate the vagus nerve, and in the MNMHT serve the same functions as nVNS devices.[43] In addition it may be that the stimulation of the vagus nerve by deep breathing is also responsible for the ability of MNMHT to reduce secondary symptoms such as osmophobia (sensitivity to smells) and possibly certain types of migraine related nausea.

These three factors in MNMHT serve as a bottom up approach to symptom regulation and affect mainly first and second order neurons in the trigeminal pain pathways, via pain gating, desensitization and downregulation. Using “body hacks” to elicit the same therapeutic effect that electronic neuromodulation devices deliver.

Non Reactive Awareness

The fourth and final main factor applied in MNMHT is a mindful, non-reactive awareness of pain.

The perception of pain is sensitive to various mental processes such as attention, and even feelings and beliefs. Mindfulness is defined here as nonreactive awareness of the present moment experience, and involved a nonappraisal and/or a nonelaborative mental stance. ^[44]

Prefrontal brain areas such as the dorsolateral prefrontal cortex (DLPFC) and the ventrolateral prefrontal cortex (VLPFC) are involved in reappraisal of the emotional significance of a stimulus resulting in a decrease in subjective pain intensity. and their interconnectivity increases over time by mindfulness training. The activity of these centers has been shown to diminish pain perception. ^[45]

More importantly the acute effect of mindfulness on pain perception acts through an activation in brain regions that mediate the cognitive control of pain, including the ACC, bilateral anterior insula, orbitofrontal cortex (OFC) and putamen, and a significant deactivation of brain regions that facilitate low-level sensory and nociceptive processing including the thalamus and periaqueductal gray matter (PAG) ^[46]

the application of mindfulness acts as a top down modulatory process that merges with the previous bottom up approach at the thalamic third level nociceptive neurons involved in migraine, to produce the remarkable effects exhibited by MNMHT techniques. This dual pronged approach means that MNMHT addresses all levels of pain perception simultaneously

Secondary elements

In addition to the primary functions of MNMHT, 3 secondary functions are used: Left nostril breathing, Abdominal massages & Spinal Manipulations.

Forced Left nostril breathing is a breathing technique prescribed by Indian yogic practices as Chandra Nadi Pranayama.^[47] It has been shown to decrease sympathetic activation of the ANS^[48]. Clinical experience has shown that Forced left nostril breathing alone may resolve an emerging migraine attack[49]. Some research points towards the involvement of an Autonomic imbalance as a contributing factor in migraine, whereby a chronic sympathetic activation causes depletion of neurotransmitters such as norepinephrine leading to migraine.^[50] Forced LNB is utilized in MNMHT in order to facilitate sympathetic deactivation and parasympathetic activation which counteracts the processes underlying migraine in those cases where sympathetic exhaustion is involved.

The second, secondary function of MNMHT is based on two types of abdominal massage, the first is performed directed to stimulating gastric emptying, and the second massage is directed to generally improve gut motility and peristalsis. The abdominal massages in MNMHT is suggested to serve the purpose of activating pain regulating functions of the Vagus nerve, mediated via the activation of the enteric nervous system. And to affect the brain in as of yet ununderstood mechanisms of migraine triggering neuropeptide transportation via the vagus nerve.

Finally the spinal adjustments in MNMHT are designed to relieve skeletal tension that translates into chronic neck pain, as well as releasing psychological tension, somatized^[51], that may contribute to chronic stress and migraine susceptibility.

Conclusion

The MNMHT is a modal method for migraine relief, that is based on the newest developments in migraine medicine, the purpose of MNMHT is to make use of the same therapeutic pathways as have been discovered, but using a physiotherapy methodology to achieve them. MNMHT replaces electrical stimulation with manual stimulation to achieve the neuromodulatory pain relief.

While electric neuromodulation devices are limited to specific nerves, each one only addresses a part of the complex system that involves migraine. The rationale behind the multifaceted approach of MNMHT is that since pain perception involves a highly distributed network of brain mechanisms, it would be required to address multiple aspects of this network in order to achieve viable results.

MNMHT is adaptive and addresses every aspect of migraine that we are able to achieve at this time. MNMHT is constantly developing and further research and clinical experience is adding more knowledge to this new form of therapy.