THERAPY OF MIGRAINE AND RELATED HEADACHES

RELATED APPLICATIONS

[0001] This application claims priority to co-pending U.S. Provisional Application No.

61/344,067, filed May 17, 2010, the disclosure of which is herein incorporated by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present invention is directed to methods and devices to treat pain and chronic recurrent migraines and related headaches, such as severe myofascial pain, cluster headaches, cervciogenic headaches, and headaches associated with fibromyalgia, in some embodiments, methods to treat chronic severe tension and related headaches, recurrent cluster headaches, migraine and associated headaches, or photophobia are described. The methods and devices disclosed herein can be used to treat headaches in classes 1 to 13 of the 1988 Headache and Facial Pain Classification System by the international Headache Society are described.

[0003] Some embodiments of the method and devices comprise surgically implanting a device through a micro incision in the subject's skin. In some implementations, the device causes a fixation of the subject's dermis and muscle elements to the subject's bone, which desensitizes the trigeminal nerve. In other embodiments, a subject suffering form a headache or related disorder can self-administer an acupuncture like and related therapy for the purpose of aborting the headache and treating the associated pain. Stimulation of the trigeminal and cervical nerve repeatedly results in desensitization of sensory nerves of the head and neck which aborts extreme sensitization of the peripheral central nervous system, pain inter neurons within thalamus and related structures involved in causing severe migraine pain. The strategic, timely application self administration of an acupuncture like stimulation allows for a safe minimally invasive non pharmaceutical based therapy to abort and mitigate migraine pain. T he devices described herein allow for a convenient form of therapy without systemic side effects which promotes self-sufficiency for the patient, and timely applications during the early and later stages of the episodic headache condition.

BACKGROUND

[0004] Migraine and tension headaches are some of the most common afflictions experienced by the human race. Migraine has been thought to occur in 20% of the female population. Migraine is the most common cause for employment absenteeism, only behind the common cold and flu. The pain associated with migraine can be severe and devastating, causing complete incapacitation. Other headache syndromes related to migraine can include cluster headache, atypical facial neuralgia, temporomandibular joint disease, myofascial pain headache, fibromyalgia, sinus migraine, as well as many other forms of headaches not associated with structural or pathologic lesions listed in the International Headache Society (1HS) Classification of human headache disorders published and referenced herein.

[0005] The migraine is characterized most specifically as a recurring, intermittent, episodic headache lasting usually between 4 and 72 hours, most often associated with photophobia (light sensitivity), phonophobia (sound sensitivity), pain worsening with movement, severe throbbing elements often unilateral, and most often associated with some element of nausea and sometimes repeated vomiting. The severity of the pain often causes cessation of routine daily activities and occasionally leads to emergency room visits for the use of parenteral narcotics or other pain relieving drugs. The temporal headache is often recurring. The intensity of the problem often depends on the number of headaches experienced by afflicted individuals. This can range anywhere from several a week to one or two a year. When migraine occurs frequently upregulation of peripheral nociceptors and central pain centers in the brain can lead to the occurrence of chronic daily headache associated with the episodic migraine, leading to almost a permanent form of headache disorder. Most often there is a prodromal period present in which the patient feels an impending headache is about to initiate prior to actually experiencing any degree of pain. This prodromal period is important to the application of the invention described herein, in that it allows the patient a signal to the onset of the headache, and the opportunity to apply therapy to abort the full evolution into an explosive headache. This period can occur over a period of minutes to hours. About 15% of afflicted patients actually have what is known as a true aura, usually seeing flashing lights which may precede the pain. The prodrome and the aura allow again for the opportunity for the institution of abortive therapy to prevent the initiation of the severe, painful phase of the headache.

[0006] Treatment can involve addressing the severe pain with analgesics. When the pain is extreme the use of narcotics, such as codeine, OxyContin, Oxycodone and Demerol, or nonsteroidal anti-inflammatory analgesics (NSAIDs), such as Toradol, can be used. Other medications used include barbiturates (eg Phenobarbital, Furocet). These medications are sometimes associated with the use of ice packs. Narcotic medications can be addicting if used frequently. They often promote nausea, which aggravates the preexisting tendency for nausea which occurs with migraine.

[0007] There are abortive drugs in the classifications of medications used to treat migraine, such as the use of Ergot alkaloids which can be given orally, nasally, intravenously, or rectally. Abortive therapy has most recently added the triptans, which are given by mouth in the form of a pill, nasal spray, or self administered injection, into the arm or thigh. The use of imitrex (sumatriptan) was the leading drug in this category of families. These drugs are serotonin acting, working on activating 5HT3 receptors. The 5HT3 receptor has been associated with the mechanism of action of the triptan family. Agonist agents have been established in mitigating migraine headache. Side effects of triptan drugs have included cardiovascular events including arrhythmias, coronary vasospasm, possible myocardial infarction, and even death.

[0008] Another category of medications used has been prophylactic therapies, which are usually given on a daily basis to decrease the frequency of the headache disorder. These are not drugs generally given during the episode, but are given on a regular basis. Such medications can include, but are not limited to the use of aspirin, antiseizure drugs such as Neurontin, methylsergide, beta-blocking agents, anti calcium channel blockers such as verapamil, and tricyclic antidepressant drugs such as amitriptyline and nortriptyline. These drugs have been also associated with side effects. Most recently the use of botulinum toxin has been used as a prophylactic agent because of its long duration of action, 3 to 4 months. This drug is injected through the skin and the forehead and temporal and posterior cervical region which also has been shown in a number of clinical studies to be protective against frequency of headaches. This drug is under current FDA phase 3 trials, sponsored by Allergan pharmaceuticals. It is designed to achieve approval as a prophylactic agent.

[0009] Over the counter medications have classically been used to treat migraine headaches and other forms of headaches. These are most available to patients and include drugs such as Indocin, aspirin, Motrin, and other drugs known as nonsteroidal, anti-inflammatory agents. These agents usually work on the prostaglandin synthesis system, which helps relieve local release of prostaglandin and related mediators which can be involved in sensitization and inciting pain. These pharmaceuticals are not very effective in severe migraine or chronic daily muscle tension headache. Some of these agents when used chronically can be associated with rebound headache if stopped; therefore a functional addiction can occur.

[0010] The use of triptan related abortive agents has been associated with cardiovascular complications (arrhythmias, vasospasm, chest pain, possible myocardial infarction). The triptan family can be used as an oral pill, nasal inhaler, or as a self administered injection. Another abortive agent class includes the ergot alkaloids. These agents have also been associated with vascular complications inclusive of cardiovascular complications, coronary vasospasm, peripheral vasospasm and gangrene.

[0011] Another class of anti -migraine therapy include the prophylactic drugs. Beta blockers are among the best known which include propranolol and timolol. Beta-blockers have been associated with inducing asthma and blocking the natural release of insulin during hypoglycemia. Antiseizure agents, such as Neurontin, Depakote, and Topamax have also been associated with side effects. Verapamil can cause constipation, fatigue, muscle pain. Topamax can be associated with weight loss and changes in appetite, and Depakote, approved for migraine headache prophylaxis, has been associated with birth defects, a serious complication given that migraine headaches are most commonly encouraged at chiidbearing age of a woman's life. The tricyclic antidepressants are associated with dry mouth, constipation, visual blurring, as well as other autonomic side effects. Fioricet and Fiorinal are often prescribed medications which contain phenobarbital. Barbiturates are an addicting form of drugs, and the chronic use of these medications can lead to, as with the narcotics, an addiction problem to these agents. The corticosteroids have been occasionally used as prophylaxis; these also have many side effects inclusive of fluid retention, osteoporosis, psychic changes, GI disturbances, skin changes, and reconfiguration of body fat. In essence all oral agents used to treat human headache disorders on a chronic basis have had some degree of side effects and again can often be ineffective.

SUMMARY OF THE INVENTION

[0012] Embodiments of the invention described herein are directed to novel methods and devices for treating pain and headaches.

[0013] In one embodiment, a method of stimulating the trigeminal nerve branches to achieve desensitization involves the use of an implant which tethers dermal and attached facial muscular elements to underlying bone. In one embodiment, the implant can be placed with a micro incision in the region of the scalp, forehead, brow, occipital area, face, posterior auricular region with the intention of attaching muscular and dermal elements to bone. In preferred embodiments, during natural facial movements, alteration in the sensory nerves produced by this type of fixation can serve to desensitize the trigeminal nerve to provide for a spontaneous, constant effect not requiring self stimulation or any conscious effort by the patient treated for migraine or related headache disorders. In preferred embodiments, with natural facial movement and facial expression, this type of tissue tethering decreases photophobia, an important component of the migraine syndrome.

[0014] In some embodiments, an implant is fixated to bone and may be applied in regions not containing critical vessels and motor nerves to avoid complications of hemorrhage or paralysis. In some embodiments, the effect will create an internal type of neurogenic inflammation mimicking the triple response of Lewis, involving stimulating and desensitizing the trigeminal nerve, so that this nerve would be less prone to contribute to sensitization in conjunction with central nervous system sensitization within the thalamus and related brain structures so that evolution of migraine pain is mitigated or aborted.

[0015] In one embodiment of a component of a method of migraine treatment, a 3-10 mm, preferably a 3-7 mm screw, and most preferably a 4-5 mm screw is placed in certain areas of the forehead, brow, face and scalp to provide dermal muscle fixation and stimulation of trigeminal nerve sensory elements using a tightly fixating wrench through 1-2 mm incisions impaling dermal elements, muscular elements and placing a tight fixation by compressing these elements firmly against underlying bone. In certain embodiments, the screw is titanium. Minimal closure effort is made with one or two sutures. During the healing process, the fixation creates an altered sensation and a sensory stimulus simulating self administered pressure or stimulation often applied by the patient who suffers from migraine or related headaches.

[0016] One implementation is most useful in treating those afflicted with chronic recurrent headaches making intermittent self stimulation on the skin surface difficult and likely effective because of frequent applications. Migraine patients with frequent attacks often undergo central sensitization which can not easily be treated by self stimulation during the prodromal periods, so that a more robust method of stimulation requiring this fixation implant who be a preferred method of therapy. This application would be best applied in migraine with severe chronic daily headaches or severe forms of chronic myofascial headaches.

[0017] In certain embodiments, the screw and/or pin placement can be anywhere along the facial bone, but most preferably in the periorbital area. The pin can be placed at angles or variable depths to achieve maximal effect or sensory nerve stimulation. Pin placement in close proximity to the supra-orbitai nerve gives maximal stimulating effect. Pins once surgically placed may be stimulated by external devices (for example, electrical or ultrasonic devices or their equivalents as is known in the art) to enhance effects on sensory nerve stimulation.

[0018] In certain embodiments, a method for treating chronic recurrent migraine or related headaches in a subject comprises surgically implanting a device through a micro incision in the subject's skin. The device causes a fixation of the subject's dermis and muscle elements to the subject's bone, which desensitizes the trigeminal nerve. In certain embodiments, a method for treating chronic severe tension or related headaches in a subject comprises surgically implanting a device through a micro incision in the subject's skin. In certain embodiments, a method for treating recurrent cluster headaches in a subject comprises surgically implanting a device through a micro incision in the subject's skin. In certain embodiments, a method for treating recurrent migraine and associated headaches in a subject comprises surgically implanting a device through a micro incision in the subject's skin.

[0019] In certain preferred embodiments, the device comprises a metallic screw, and the method further involves compressing the subject's soft tissues to the subject's bone with engagement of the screw to the bone. In certain preferred embodiments, the metallic screw is titanium and measures between 4-5 mm. In certain preferred embodiments, the metallic screw is stainless steel. In certain preferred embodiments, the metallic screw is magnetic.

[0020] In certain preferred embodiments, the device is implanted in multiple locations.

[0021] In certain preferred embodiments, the related headaches are severe myofascial pain, cluster headaches, cervciogenic headaches, headaches associated with fibromyalgia, or tension headaches.

[0022] In certain preferred embodiments, the method involves application of ultrasonic or electronic energy to enhance stimulation of the trigeminal nerve. [0023] In certain embodiments, the invention is directed to a method for treating photophobia in a subject by implanting a metallic device fixated to bone in proximity to the subject's facial sensory nerves,

[0024] In certain embodiments, a method for treating and aborting pain associated with migraine headache comprises identifying the prodromal stage of the headache, applying a device which causes a measured skin surface penetration or surface distortion by one or more micro needle or micro blades to skin of the scalp, forehead face, or neck region during the prodrome for a for a defined period to cause skin erythema, irritation and a small degree of skin edema a defined period. In certain embodiments, the migraine syndrome includes a tension headaches or chronic daily headache component.

[0025] In certain embodiments, the device further contains a mechanical forced system which allows for a measured penetration to occur automatically. In certain preferred embodiments, the prodrome is identified by afflicted persons and the device is self applied. In certain embodiments, the prodrome period is defined prior to the onset of severe pain.

[0026] In certain embodiments, the time period ranges from 2-2,000 seconds. In certain embodiments, the depth of penetration is between 100-1000 microns. In certain embodiments, the location of application is single or multiple areas of the head and neck. In certain implementations, the mechanical force system is a spring loaded system, an electronic actuator, a manual push system, a self loaded hydraulic system, or equivalent systems.

[0027] in certain embodiments, the application may be repeated one or more times.

[0028] In certain implementations, sterile micro needle or micro blades are detachable from a delivery device. In some embodiments, a needle is a compressible synthetic which causes distortion of skin but does not penetrate into the dermal layer of the skin. [0029] In certain embodiments, a device for aborting or reducing headache pain associated with migraine comprises a series of measured needles tips, micro blade, or pins mounted on a compression platform capable of penetrating or distorting skin to cause a small wheal, and flare when applied in one or more regions of the head and neck. In certain embodiments, the device provides a force generator to allow self application of measured needle tips, micro-blades, or compressible synthetics to skin and creates a small non-scarring penetration or distortion so repeated application is possible. In certain embodiments, the device remains attaches to the skin for a fixed period.

[0030] In certain preferred embodiments, the device includes needle tips or micro blades are made of stainless steel or titanium. In certain preferred embodiments, needles, micro blades or compressible devices are sterile disposable units. In certain embodiments, forces can be manually self-applied, spring self-applied, hydraulic device self-applied, or electronic actuator self-applied.

[0031] In some embodiments, skin penetration is between about 50 microns and about

3000 microns, preferably between about 50 microns and about 2000 microns. In some embodiments, the compression platform is between between 2 sq mm and 2000 sq mm.

[0032] In certain embodiments, a device is manually attached to the skin. In other embodiments, attachment to skin can be by way of adhesive, fixation, band, or suction devices or their equivalents. In certain implementations, the device is disposable. In some embodiments, the device is engaged on skin. In some embodiments, a device is engaged on skin surface for between 2-2000 seconds. In some embodiments, the device is housed in earmuffs, eyeglass frames, hats, headbands, or adhesive bandages. In some embodiments, penetration elements have a diameter or thickness between about 500 to about 10,000 microns. [0033] In certain embodiments, a device for aborting or reducing headache pain associated with migraine comprises a series of one or more suction cups capable of applying negative internal pressure causing a small wheal and flare when applied in one or more regions of the head and neck and a force generator to allow self-application. In some embodiments, the device creates a small non-scarring penetration or distortion, in some embodiments, repeated application is possible. In some embodiments, the device remains attached to the skin for a fixed period.

[0034] In certain implementations, the suction cups are self applied during the prodrome of migraine or combine headache syndrome. In certain implementations, one or more suction cups applied over the head and neck region. In certain implementations, the wheal and flare constitutes the triple response of Lewis. In some implementations, the device is applied over a skin region pretreated with antiseptic such as alcohol. In some implementations, the device is left in position for a period of 2-2000 seconds.

[0035] In certain embodiments, a device for aborting or reducing headache pain associated with migraine comprises an ultrasonic stimulator which results in a triple response in one or more regions of the head and neck. In certain implementations, the device is applied during the prodrome of a migraine, does break epidermal or dermal barriers, and/or remains attaches to the skin for a fixed period during a migraine prodrome. In certain implementations, the device is applied over a skin region pretreated with an antiseptic, for example alcohol, capsaisin, or the like. In certain implementations, the device is left in position for a period of 2- 2000 seconds. In certain implementations, the device causes a triple response.

[0036] In certain embodiments, a device for aborting or reducing headache pain associated with migraine comprises means for producing a first chemical endothermic reaction followed by a second chemical exothermic reaction. In certain implementations, the device is applied during the prodrome of a migraine, does break epidermal or dermal barriers, and/or remains attaches to the skin for a fixed period during a migraine prodrome. In certain implementations, the device is applied over a skin region pretreated with an antiseptic, for example alcohol, capsaisin, or the like. In certain implementations, the device is left in position for a period of 2-2000 seconds. In certain implementations, the device causes a triple response.

[0037] In certain embodiments, a method and/or device for aborting or reducing headache pain associated with migraine comprises means for causing desensitization of the trigeminal or cervical nerves using tactile force or penetration to the skin by initiating an inflammatory response. In certain implementations, the prodromal stage of a headache is identified as a preliminary step. In certain implementations, the inflammatory response does not cause scarring upon repeated use. in some embodiments, the inflammatory response include the triple response of Lewis. In some embodiments, the inflammatory response is augmented by repeated applications and/or one or more additional pro-inflammatory agents. In some embodiments, the inflammatory response is characteristic of neurogenic inflammation and/or augmented by neurogenic inflammatory agonists.

[0038] Some embodiments of the methods and devices described herein involve surgically implantable devices, while others involve externally applied devices and methods, which may be manually accomplished. Any of the embodiments described herein may comprise desensitization of the trigeminal or cervical nerves.

DESCRIPTION OF THE FIGURES [0039] Figure 1 : Is directed to an embodiment of a self-stimulating device effective for use as in non-pharmaceutical method for the treatment of migraine headache. The figure schematically shows various parts of the exemplary device, some of which parts are optional or can be modified in various embodiments, such as an outer case, a force generator, a detachable contact, a governor, a disposable pin needle fixation device with stop plate, and a contact platform.

[0040] Figure 2: Diagram of the human skin anatomy. Superficial projections of sensory nerves are illustrated. The average thickness of human epidermis is about 2mm, although variations occur according to body region and population.

DETAILED DESCRIPTION

[0041] Therapeutic methods and devices for subjects afflicted with a human headache disorder, such as migraine or other headaches, are disclosed. The methods involves stimulation of the trigeminal nerve for the purpose of aborting the headache and treating the associated pain. The methods and devices allow for a safe, minimally invasive, non pharmaceutical-based therapy to abort and mitigate migraine pain. These devices and methods allow for a convenient form of therapy without systemic side effects.

Variants of Migraine Headache

[0042] Migraine headache is generally defined as an episodic, severe headache, lasts 4-

72 hours, and is associate with light and sound sensitivity and varying degrees of nausea and occasional vomiting. The pain is often unilateral but can be bilateral and is often worsened by movement. The variation of migraine can occur with respect to neurologic deficits seen early in the headache attack, association with other forms of headache (eg, tension headache, myofascial headache),

[0043] The variants of migraine can be often defined by vasospasm associated with the early phases of the headache, which can create transient neurologic deficits such as loss of vision or visual field, visual hallucinations, impaired speech (dysarthria, aphasia), paralysis, sensory loss, loss of consciousness, and nerve palsy (eg. oculomotor nerve palsy).

[0044] Other variations of migraine can be associated with frequent attacks which are thought, to cause a chronic sensitization of pain center in thalamus and related brain structures causing chronic daily pain, characterized as chronic daily headaches, myofascial pain, and fibromyalgia, associated with the more severe migraine syndrome.

[0045] Other variations include extended repetitive headaches over a period of weeks

(cluster headaches), facial headaches (sinus migraine), migraine associated with acute allergy (hay fever), migraine associated with menstruation, migraine associated with Horner's syndrome, retinal migraine, and food associated migraine syndrome (eg associated with consumption of wine and cheeses, nionosodium glutamate, bisulfate).

[0046] The methods disclosed herein are intended for use in many variants of migraine.

A preferred embodiment of the method is a treatment for the common migraine as defined in the international headache society classification under section 1. See Table 1. Another preferred embodiment of the method is a treatment for tension type headaches as defined in the international headache society classification under section 2.

Sensory Tactile Suppression of Headaches [0047] It has been long known that some human essential headache disorders, which include migraine, tension headache, or a combination of both, as well as cluster headaches and other headaches not associated with structural lesions of the brain that are listed in Table 1 are associated with the presence of tactile suppression. Tactile suppression involves stimulation of the forehead, usually self stimulated with digits or pressure, which relieves the pain to some degree, The common migraine patient will often press on their head or put objects on their head, such as a cold cloth, to press on their head to sustain a relief in pain. This phenomenon has also been seen with movement diseases of the face, head, and neck, such as the sensory suppression and sensory tricks associated with adult onset spasmodic torticollis and facial dystonia and blepharospasm in Meige syndrome. Self stimulation has been thought and described to suppress interneuronal activity of brain stem neurons associated with movement in these situations (see Tolosa et al). The suppression seen with human headache disorders has not been extensively studied from a neurophysiologic point of view, but likely represents a similar type of response as seen with human movement disorders. This would be interpreted as a sensory stimulation of the head and neck region and headache disorders, or suppresses upreguiated hyperactive neurons in the brain which generate the pain. These neurons probably occur in the thalamus, but has often been thought to spread to multiple areas and does not represent one specify loci. The tactile stimulation is simulated in an extreme form by the use of acupuncture.

[0048] Acupuncture has been shown to be effective in the treatment of severe pain and headaches in a clinical setting. Acupuncture in a patient with a severe headache can be relieving of the pain and mitigate the degree of symptoms. The American Academy of ophthalmology in 2003 has supported the use of acupuncture for the treatment of headache disorders based on clinical experience and some degree of studies. The disclosure of this document is incorporated herein in its entirety. See Complementary Therapy Assessment Acupuncture for Ocular Conditions and Headaches, American Academy of Opthamology, May 2003, the disclosure of which is herein incorporated by reference.

[0049] The methods disclosed herein build on the principle that acupuncture can be found to be effective in both abortive therapy and pain therapy. In abortive therapy, during the prodromal period of the migraine, acupuncture can be applied to abort the full development and evolution of the pain syndrome. Generally the needles are placed in the temporal regions of the face, hairline of the facial, temporal, and neck regions. The needles are generally placed from 1 to 100 positions, but preferably 2 to 6 needles are used in the punctures. The purpose of the placement of the acupuncture to stimulate the sensory division of the trigeminal nerve, as well as sensory branches of cervical nerves.

[0050] Certain embodiments described herein involve a self administrative device and method to accomplish and improve on the effects and goals of acupuncture. Self administration of the acupuncture affords a timely application during the prodromal period so the full evolution of the headache can be aborted. Patients who suffer from migraines often feel a prodrome but do not have the time to see a physician who is skilled in acupuncture, or an acupuncture therapist. This is also an expensive endeavor for the patient, as acupuncture generally is costly. When delays in acupuncture are applied the therapy has been thought to be, by the inventor, much less effective. Although the acupuncture can be applied during the pain period to relieve pain, the most effective and the best performance of acupuncture is as an abortive function to prevent the development of the full headache disorder. Another improvement consists of accomplishing a critical level of irritation and stimulation in order to elicit a triple inflammatory response which will augment the effects of acupuncture. [0051] In the case of migraine, the application of acupuncture is thought to suppress spontaneous neuronal activity theorized as causing the severe pain and often stimulating the nausea and vomiting typical of the migraine syndrome.

Current Therapeutic Problems

[0052] The current therapy of tension migraine headache has been usually treated pharmacologically. Dissociated side effects of these agents can be problematic for patients. These agents are often extensively expensive, require prescriptions, often require many trial and error courses of medications, and need to be renewed. The use of a self administrating device which has no systemic side effects is a clear improvement in the treatment of human migraine and related headache disorders. The use of a self administrating device has a low cost, has no substantial systemic side effects, and can be applied in repeated locations. Among professional organizations there has been endorsement of acupuncture therapy as being effective. The self administration device allows an improvement over existing administration methods which require another professional person, physician or acupuncturist to place the needles. The acupuncturist also is using the treatment to achieve prophylactic effects as the application is not synchronized with the onset of the headache during the prodrome. This approach severely reduces the impact of this modality on the course of headache morbidity. The use of a self administered acupuncture with the devices described herein solve this problem and allow a more effective application of the treatment modality, while simultaneously allowing a more convenient therapy for the afflicted. The timely application of the needle penetration synchronized at the headache prodrome allows for potentiating and improvement of needle skin puncture effectiveness in the treatment of human headache disorders. In certain embodiments, the therapy is administered during the prodromal phase of the headache so that the painful portion of the headache does not fully develop and the person afflicted with the migraine does not experience most of the pain related morbidity.

The Temporal Sequence of Migraine Headache

[0053] Common migraine is conventionally episodic in nature. The discrete severely painful episodes however can be anticipated by the suffer during the prodrome, a period in which an afflicted individual feels malaise, early nausea, loss of appetite, increasing response to sensory stimuli such as odors, sound, light, and increasing muscle tension. The prodrome usually is not associated with signifianct pain which is the most debilitating of the migraine syndrome. In a minority of patients, the afflicted may experience a visual aura consisting of flashing lights, visual hallicuination usually consisting of zig-zag lines, shimmering vision or transient blind spots. Variations occur in the prodrome experience and in visual auras. About 15 % of migraine sufferers experience a visual aura however a much larger number (>80%) experience a prodrome. The prodrome period allows the use of abortive medications and activities. Some patients use cold packs, pressing bands, warms packs, message and postures to try to relieve the severity of the impending pain trying to avoid use abortive pharmaceuticals.

[0054] Methods and devices are disclosed herein, which automatically treat headaches during the prodrome period of migraine, with the purpose of aborting a migraine headache or reducing its severity. The methods and devices, may be used during the prodrome of migraine, or may be used for other headaches listed in Table 1 in which a prodrome is experienced. [0055] Persons of skill in the art realize thai there may be an overlap in the diagnosis between migraine and tension headache. Some patients with episodic migraine will have frequent tension headaches, and some with frequent tension headaches will have migraine. Although migraine is typically associated with nausea— some migraines are not— and are instead predominately characterized by a severe intensity, a throbbing quality, and intense photophobia associated with autonomic symptoms of pallor of skin, sweating, flushing. In these situations, the headache may still be classified as a migraine. Tension headaches are generally less severe and characterized by band like tightness around the head, neck stiffness, jaw stiffness, often relieved by mild analgesics such as aspirin, indocin or other non-steroidal anti-inflammatory drags.

Peri-Orbital Tactile Suppression of Phtophobia With Benign Essentia! Blepharospasm and Fistfaer Insight into Seesory Tricks

[0056] Photophobia has been recognized as an important component of benign essential blepharospasm. (See e.g., Borodic GE Quigg C, Photophobia and Essential Blepharospasm, American Society of Ophthalmic Plastic and Reconstructive Surgeons, Annual Meeting, Chicago 1996; Adams AH, Digre KB, Bhupendra C, Patel K, Anderson RL, Warner JE, Katz BJ ₃ The evaluation of light sensitivity in benign essential blepharospasm. Am J Ophthalmol 142:82-87, 2006: Herz NL, Yen MT, Modulation of sensory photophobia in essential blepharospasm with chromatic lenses, Ophthalmology 112:2208-2211, 2005; Borodic GE, Acquadro M, Johnson E., Botulinum toxin for the treatment of pain and inflammation. Expert Opin Investig Drugs 10(8): 1531-1544, 2001, the disclosures of which are incorporated by reference herein in their entireties). The incidence of this symptom is present in over 80% of patients, and is often noted to be particularly severe during exacerbations of this chronic disease. Relief has been traditionally achieved by patents with a filtering lens, and more recently, with use of specialized filtering lenses which are more absorbing in the shorter wavelength spectrum. Additionally, patients have related increased light sensitivity with the need for repeat botulinum toxin injections after 10-12 weeks, and many note improvement in photophobia with subsequent botulinum toxin administration. The use of botulinum toxin for the treatment of migraine and other forms of essential headaches, both often associated with intermittent and sometimes chronic photophobia, has been extensively studied with successful results in many but not all studies. From these observations, it is reasonable to induce possible relationships between photophobia and the basic neural mechanisms underlying eyelid involuntary movement disease and possible treatment effects.

[0057] The "sensory trick" is a common behavior in the bilateral blepharospasm and

Meige syndrome patient. Typically, a digital effort is made unilaterally with elevation of the brow causing the eyelid to stay open long enough to improve visual function. Both the patient and the examiner initially interpret the behavior as simply prying open an eyelid afflicted with involuntary spasmodic movement to obtain vision. This explanation, however, is incomplete because the maneuver benefits contralateral eyelid movement and creates a sensory change. Elevation of one eyebrow results in improvement in blepharospasm in the contralateral eye may provide some insight into disease mechanism. Usually, the sensory trick is location specific and unilateral for each patient, improvement in the contralateral eyelid is clearly not mechanically based, but rather, is dependent on the suppression brainstem function or other central nervous system structures governing the blink reflex, in other medical centers, stimulating devices have recently been tried to improve control of eye movements mimicking the self-administered tactile effort. [0058] Using studies involving the trigerninal-facia! motor reflex, Tolosa et al. described increased length and amplitudes in the R2 wave measured in the orbicularis contralateral to the stimulated side stimulated side in patients with essential blepharospasm, and interpreted these findings as representing a population of unstable brainstem interneurons governing spontaneous blinking. These authors have subsequently demonstrated the effect of tactile stimulation of the brow causes a suppression of these R2 wave abnormalities. Others have demonstrated suppression of the R2 waves using repetitive peri-orbital electrical sensory stimulation. However, before this disclosure, no author has recognized or described the tactile effect on subjective visual perception of brightness. See Hallet M, Evinger C, Janovic J, Stacy M. Update on blepharospasm: report from the BEBRF International Workshop. Neurology. 2008;71 :1275-1282; Tolosa E, Monsterrat L, Bayes A. Blink reflex studies in focal dystonias: enhanced excitability of brainstem interneurons in cranial dystonia and spasmodic Torticollis. Mov Disord. 1988;3:61-69; Gomez-Wong E, Marti MJ, Cossu G, Fabregat N, Tolosa E, VallsSole J. The 'geste antagoniste' induces transient modulation of the blink reflex in human patients with blepharospasm. Neurosci Lett. 1998;251 :125-128; Gomez-Wong E, Marti MJ, Tolosa E, Valls-Sole J. Sensory modulation of the blink reflex in patients with blepharospasm. Arch Neurol. 1998;55: 1233-1237; and Sommer M, Ferbert A. The stimulus intensity modifies the blink reflex recovery cycle in healthy subjects and in blepharospasm. Clin Neurophysiol. 2001 ;112:2293-2299, the disclosures of which are herein incorporated by- reference.

[0059] From observations and patient interviews, it was observed that the sensory trick suppresses photophobia. Patients having a strong predisposition to brow and periorbital self stimulation relate an almost instantaneous decreased in light sensitivity which usually correlates to reduction in intensity of symptoms. The reduction can be demonstrated when light intensity is increased in either eye, that is, in the eye receiving the tactile stimulation and in the contralateral eye. The reduction in photophobia ceases simultaneous on withdrawal of tactile stimulation. This phenomenon was observed in a series of 18 cases of essential blepharospasm and Meige disease. That observation contributed to the theory and motivation for implantation of self drilling titanium fixation screws (fixation pins) for both partial orbicularis restrictive immobilization and sensory augmentation over the trigeminal nerve during routine facial movements. The sensory augmentation may suppress blink interneurons simulating a sensory trick. Patients with implantable metallic pins around the orbital rim causing orbicularis fixation improve with respect to both blepharospasm and photophobia over a sustained period. The pins cause a slight increased sensitivity to the brow region as well as alter movement pattern of facial muscles with attendant alteration in proprioception in the region. The success achieved with this procedure lends credibility to the notion that certain facial movement disorders may be altered by manipulating certain afferent sensory inputs and that there is significant interplay between visual and somatic sensory systems causing this condition.

[0060] Without being bound by theory, it is believed that the mechanism for tactile suppression of photophobia potentially relates to suppression of centers in the brainstem receiving extra geniculate retinal projections governing the sensation of brightness and involuntary and automatic eyelid closure. Such neurons may be associated with pretectal region known for regulating the pupillary light reflex and along retinal projections into brainstem regulating automatic eye tracking and lid movements. [0061] Although migraine is a different syndrome than essential blepharospasm, similarities in the benefit of tactile stimulation is apparent for both conditions, and the morbidity of both conditions can be viewed as a result of sensitized central neurons. In the case of blepharospasm, hyper excitable sensitized neurons control blink movements, whereas in the case of migraine, sensitized neurons govern pain perception and are located in the thalamus and associated regions. A needle stimulator causing the triple response of Lewis has been noted to improve both migraine pain and abnormal blink movements associated with essential involuntary neurologic blepharospasm.

[0062] Both conditions (migraine and blepharospasm), can be treated with various embodiments of the methods and devices described herein. The methods and devices can be used on one or more locations of the head and/or neck, and can be applied for various time intervals, for example for 1-60,000 seconds, preferably 60-600 seconds. Moreover, photophobic migraine and other chronic headache sufferers are expected to be an important selection criterion for use of embodiments of the methods and devices described herein.

Light and the Generation of Migraine and Related Headache Pain

[0063] Photophobia is a well appreciated component of the migraine and tension headache syndrome. During periods of severe pain, light is perceived as uncomfortable and very annoying. Patients often seek a dark room to enhance comfort.

[0064] More specifically, light intensity has been perceived to make the headache worse.

Without being bound by theory, this observation indicates that the perception of light plays a role in the generation of migraine headache pain, and that light sensitivity may not just be an epiphenomena. Retinal projections into the brain pass through the geniculate body are generally appreciated as image related signals which project to occipital cortex and associated brain areas that process and recognize images. Retina ganglion cells also project through extra-geniculate regions of the brain which effects changes in papillary size and papillary light reflexes, blink, and circadian rhythms. In these regions, thalamic pain centers can integrate information on light intensity and light signal intensity can aggravate excitability of thalamic pain neurons associated with migraine. Hypothalamic functions are closely associated with extra geniculate retinal signaling as well as regulation of hormonal menstrual cycles via release of small peptide release factors into the pituitary gland. Migraine is much more common during early menstruation than any other time of the cycle, indicating a neuro-endocrine link to the pathogensis. As disclosed herein for the first time, it was unexpectedly observed that stimulation of the scalp brow and forehead region can consistently depress photophobia associated with a facial movement disease know as benign essential blepharospasm and Meige syndrome. Self administered pinprick eliciting a triple response of Lewis was especially effective in depresses and temporarily eliminating photophobia in this condition. These movement diseases are also associated with hyperexcitable brainstem interneurons.

[0065] Without being bound by theory, and by using a logical mathematical substitution of phenomena, it is disclosed herein for the first time, that self administered pinprick can create depression of hyperexcitable interneurons caused or aggravated by light stimulation as projected through extra-geniculate pathways from the retina. The generation of the migraine syndrome is no doubt multifactorial, however, dampening the sensitization by depressing light sensitivity appears to be important in mitigating pain.

[0066] Prior to this disclosure, the association between somatic stimulation and light sensitivity from the human eye in certain pathologic conditions has not been made. The inverse relationship is pivotal to the practice of the invention as stimulation using tactile devices, increased stimulation using a penetrating needle or microblade (which in one embodiment can be an implantable device, for example a metallic screw) eliciting a triple response of Lewis which functions to enhance the suppression of light sensitivity. This in kind decreases sensitization of centra! pain neurons. Treatment of photophobia by somatic sensory stimulation in order to abort migraine and related headaches is accomplished using embodiments of devices and methods described herein.

Exemplary Self-Administered Device:

[0067] In one embodiment, a device capable for creating an automatic standardized pinch, small puncture, in one or more location of the scalp, temporal region, mid face region neck region scalp region is disclosed. The device can optionally be independently operated by the afflicted during the critical prodrome period in an effort to abort the full blown migraine with severe pain. The device will consist of several general components, some of which are opotional. Variations of the components and their equivalents are within the scope of this disclosure, variation is possible.

[0068] In some embodiments, the components may include one or more of the following: a platform for contain with head and neck skin covering a define area; a moving component with pointed deliver needle, pins, mini-blades; a housing for the moving component to slide in the direction of the skin; a force generator (manual, electric actuator, spring loaded, hydraulic) which causes force and energy transferred to the moving component; and/or a governor which allows a reproducible limit the degree of skin penetration by micro needles, pins, or mini-blades. Various components are represented schematically in Figure 1. Figure 1 is given by way of example, not by way of limitation. The device uses a "tactile stimulation unit," for example needles, pins, micro needles, micro pins, or their equivalents or the like. A primary purpose of the tactile stimulation unit is to create a sensory stimulation over the dermatomes (sensory segments) corresponding to projections of the trigeminal nerve and cervical nerve roots. The sensory stimulation is created by a partial thickness needle penetration of the skin sufficient to penetrate the epidermis, full thickness penetration of the skin, or an irritating compression of the skin by- blunt stimulation. For each category of stimulation, a response characterized by erythema, edema, and mildly unpleasant discomfort is created, that is, a triple response.

[0069] In general, the platform should be placed flush to the skin and even to a point capable of causing doming of the skin. The platform may be hollow easily allowing doming or contain at ledge to facilitate doming. Another embodiment of the platform design shall include a convex or flat platform which allows close contact with the skin. The size of the platform can vary from several square mm to 50 sq mm, but preferably 2-10 sq mm. Larger platforms are possible. It is anticipated in a preferred embodiment that the size of the platform be defined by the diameter of the device.

[0070] In general, the moving component shall function as a platform to fixate and stabilize one or more needles, micro needles. Pins, micro blades, or needles attached to the moving component shall be automatically or manually directed toward the skin once the platform is immobilized secured to the skin surface. Movement of the device during penetration may produce unnecessary skin abrasions and scratching. The moving component may be able to sustain axial free rotation in order to avoid unnecessary abrasion after penetration or stimulus delivery. The moving component shall in one embodiment comprise a deposable platform which may be screwed, clamped, or temporarily attached to the force generator so the delivery can be repeatedly used in a sterile fashion, with replacement of the needle platform to maintain sterility. Needles may vary from 38 gauge to 14 gauge, may be solid or hollow, beveled or conical, and may be made of stainless steel, titanium or hard plastics. In situations involving a non penetrating stimulation device, the materials can vary from rubber, plastic blunt metal, nylon, prolene, or other forms of synthetics. The needle microblades should contain a limitation platform at the based to provide for limited and controlled penetration depth. This limitation platform shall be similar to a surgical step blade used for partial thickness incisions into the eye wall (sclera) and cornea for cataract surgery.

[0071] In some implementations, the housing shall consist of a hollow cylinder, square or rectangular configuration, or other configuration which may launch and direct the moving component toward the skin. The configuration of the shaft shall be not limiting, but should be easily held in the hand of the afflicted person self applying the stimulation or another person providing the stimulation. In designs which provide for rotation of the needie-mierob!ade platform, the housing may contain a rotation fulcrum pivot (similar to a secretary's signature stamper) so that the needles are not loaded downward but upward, providing for no needle exposure. The delivery shaft may also contain a restriction platform which provides for limitation of needle micro-blade penetration.

[0072] In some implementations, the force generator can be manual, electric, spring loaded or hydraulic or other equivalent variations or combinations of the like that are capable of pushing a needle into skin in a controlled fashion. In one embodiment, the needles-micro-blade device is pushed manually against a spring to a point built into the shaft of the device. The stop point represents one safety measure to limit needle penetration, while the platform on the needle, micro-blade device provides the most effect stop for needle penetration. The spring functions to retract the partial skin thickness penetration when the user wishes to terminate the cutaneous stimulation. In another embodiment the spring action is in the opposite direction which lafter manual load, the spring functions to create the penetration of the needle microblade device therefore causing the stimulation, much like a auto-injector system used to self apply epinephrine or other self administered drugs. An air or gas loaded hydraulic system or electronic actuator can accomplish the same purpose.

[0073] In one implementation, the penetration governor shall be designed in one or more positions in the device. The platform at the base of the needle or micro blade or the materials (soft vs rigid) shall provide some safety as to the degree of penetration. The extent of the movement of the needle micro-blade platform down the shaft of the device shall also provide control of penetration. In preferred exemplary embodiments, penetrating elements shall be about 500-10,000 microns in diameter, and shall penetrate between about 50 microns and about 4,000 microns on impact with skin.

[0074] The human skin anatomy is depicted in Figure 2, Figure 2 depicts the superficial projections of sensory nerves. The average thickness of human epidermis is about 2mm, but it varies over the body surface, and varies from person to person.

Triple Response of Lewis.

[0075] Embodiments of the devices and methods disclosed herein produce a physiologic reaction along cutaneous nerves involving the release of inflammatory mediators from sensory nerves and related cells involved in neurogenic inflammation. Release of histamine, serotonin, neurpeptides, and cytokines occurs upon needle or scratch stimulation of skin. This response is classically defined as the physical sign of wheal and flare. The wheal is an edematous papule surrounded by a red discoloration. A sensory experience characterized as an itch, prickleing sensation or scratch is often experienced and is anticipated to be created by the method and devices described herein.

[0076] The neural stimulation created is mediated by dendritics projection of the sensory component of the trigeminal nerve which carries signals into the central nervous system ganglia and projects into the brainstem via intemeurons. The interneuron integrates into pain centers within the thalamus and related brain regions. The central nervous system pain receptor neurons within the thalamus and related structures adapts to continued impulse generation by the skin by an increase in activation thresholds (decrease sensitization). The decreasing sensitization of central nervous system pain receptive centers represents the effective mechanism by which tactile stimulation can be useful for the treatment of migraine and related headaches.

[0077] In patient with migraine, physiologic changes occur in the central nervous system pain centers, which increases the responsiveness (nociceptive) of the thalamic and related brain structures, which leads to an increase of perceived unpleasant responses to non-noxious stimuli. For instance, regular light intensity is percetived as extensive uncomfortable brightness (photophobia), normal sounds are perceived as exceptional and unpleasantly loud (phonophobia). Regular body movement with positional sensory signals are interpreted as painful, often worsening the headache. Migraine patients essentially suffer from a transient central nervous system sensitization which causes non-noxious stimuli to be integrated by the persons afflicted as painful and unpleasant. During the full blown migraine experience, the person is often seen in a dark quiet room, immobile in bed covering their head. [0078] Implicit in the method defined herein is the interplay between peripheral trigeminal and cervical nerve physiologic changes in migraine and thalamic pain center sensitization. Maladapted activity at both levels is needed for the increasing crescendo of pain and morbidity associated with the migraine attack. Stimulation of the trigeminal and cervical nerves by eliciting a triple response results in a desensitization of the trigeminal and cervical nerves which results in an effective block in the peripheral nerve -thalamic interplay responsible for the evolution of the pain syndrome. The needle micro-blade punctures eliciting a triple response essentially desensitizes the peripheral nerve, which in turn, mitigates acute central nervous system sensitization. In cases of chronic central nervous system sensitization, the effectiveness of a needle micro-blade puncture or any other method of eliciting a triple response is less effective in relieving pain. However, some therapeutic effectiveness is still possible.

[0079] Although in many embodiments of the invention, needle or micro blade penetration is needed, other methods are available to elicit a triple response of Lewis which causes initial stimulation followed by sensory nerve desensitization. For instance, in one embodiment, suction cups in one or more locations can be applied for a defined period of time in order to produce skin irritation erythema, and minimal edema. An advantage to this approach would be lack of penetration of dermis which could produce an infection risk. Suction cup penetration can be used with topical preparations of capsaisin, a stimulator of neurogenic inflammation, which can be an agonist effect of the mechanical devices, causing peripheral nerve desensitization by effecting neurotransmitter depletion. Neurotransmitters depletions can include neuropeptides, histamine, serotonin, prostaglandins related autocoids, leukotriene related autocoids, CGRP, nitrous oxide, glutamate, acetylcholine, substance P, and various other cytokins. Practicing the nerve stimulation for the relief of headache pain should not be limited by theory involving mechanisms of nerve sensitization or desensitization. In an another embodiment, pinching micro clamps can be applied which cause a pressure induced inflammatory response characterized by erythema, irritation and minimal edema can be used to stimulated sensory nerves of the head and neck region to treat eminent headache pain, in still another embodiment, a high frequency vibrating device sufficient to cause edema, erythema, and minimal irritation can be used at the prodrome of the headache to abort the eminent painful phase. Other embodiments which stimulate sensory nerves are within the scope of this disclosure.

Use of the Exemplary Self- Applied Devices

[0080] The devices described herein, when self-applied during the prodrome of a migraine or related headache disorder, create a sufficient stimulation of sensory nerves of the head and neck to cause sensory nerve adaptation and eventual desensitization. The duration of time to create such an effect to abort or mitigate to intense pain associated with essential headache disorders such as migraine or severe tension headache can vary, but will be of the order of about 1-60,000 seconds. During this time period, consistent stimulation of the sensory nerve is achieved to abort central nervous thalamic and related structures from being sensitized. Signs of central nervous system sensitization include the sensation of nausea (often followed by vomiting) so common as part of the migraine syndrome. A secondary effect of applying the nerve stimulation using a device which causes a triple response in one or more locations will be to mitigate the nausea and vomiting associated with migraine. A successful treatment to abort this stage of the headache is not only predictive of eminent pain mitigation, but therapeutic as an antiemetic effect. [0081] The device can be fixated to the scalp manually by the afflicted, with a headband, with a suction device, glue or taping system, a clamping system, or other equivalents means, or may be fixated by another person, such as a medical professional or Say person. The device ideally can be conveniently sized to fit in a clothing pocket or purse.

[0082] Pretreatment of the skin with alcohol, acetone, capsaisin or other irritates are possible to augment the degree of neurogenic inflammation and sensory nerve stimulation elicited by the device.

[0083] The methods and device can be applied one or more times, and applied to one or more regions of the head and neck.

Variations in Housing of the Device:

[0084] In various exemplary implementations, the device may involve a wrap around band, hat, glass frame equipped with micro needles, micro blades or other irritating component able to elicit a triple response of Lewis. Each of these devices shall have a method to produce force and controlled depth of penetration through skin of one or more needles, micro blades, or other irritating component able to elicit a triple response on the skin and therefore stimulated the trigeminal nerve.

[0085] In one embodiment, the irritating device is in the ear support arms of a pair of conventional eyeglasses capable of generating an irritation or micro penetration through skin to effectively desensitize the trigeminal nerve. The arms may contain a spring load force generator, electronic actuator, hydraulic device or manually driven device to create a skin triple response. Such devices may also be contained within a pressure band, hat, visor, headband, or hairpiece. Another variation of the device mounting shall be in the form of earphones where the penetrating and stimulating elements are in the peripheral mountings and contact pieces around the ears. The earphone arrangement allows for a posterior and hairline location of stimulation to achieve the triple response and trigeminal nerve stimulation followed by desensitization, A neck piece stimulation device may be arranged so that posterior cervical stimulation and penetrating elements may be used where posterior cervical stimulation is usual for treating the migraine. Another method of housing the pin, micro blade needle stimulators is an adhesive bandage. As bandages are more familiar, a bandage and penetrating or irritating component is placed under a bandage followed by manually applied pressure, or pressure from a headband device, so that the triple response of Lewis can be elicited.

[0086] It is anticipated that the use of multiple devices may be preferable in certain cases to treat large regions of the head and neck. For instance, a forehead stimulator followed by an earmuff stimulator, and so on.

Exemplary Non-Penetrating Embodiment of the Deviee

[0087] Another embodiment comprises of a non-penetrating skin stimulator which elicits a triple response of Lewis during the prodromal stages of migraine and associated headaches which causes desensitization of the trigeminal nerve which results in mitigation or complete cessation of migraine pain. This device will scratch, pinch, and'Or create suction pressure to a degree necessary to elicit a triple response on the skin. Components effecting this response can be accomplished with a suction cup, stiff brush with rubbing element, soft tissue pinching device, vibrating devices, chemical devices, ultrasonic devices. Each device in the non penetrating category shall be applied only during the prodromal stage of migraine, in an intensity and power-energy level to produce a triple response during the prodromal stages of the migraine. [0088] In yet another embodiment, a chemical device would use thermal changes occurring from evaporation followed by application of heat. Swings in service temperature over a short period of time can cause vasulature reaction couple with other chemical irritants which can elicit a triple response.

[0089] As with penetrating blades, needles and micro needles, embodiments of nonpenetrating skin stimulators are directed at causing a desensitization of the trigeminal nerve, so that rapid sensitization of thalamic an associated brain centers mediating the pain experience is aborted.

[ΘΟ90] Non penetrating devices may be placed in any area of the head or neck, but are preferentially placed on the forehead, scalp, poster auricular region and/or the back of the neck. These devices may be placed over multiple regions and for varying lengths of time. The stimulation produced by these non penetrating devices may be enhanced by use of alcohol, capsaicin, camphor, or other skin counter- irritants.

[0091] The non-penetrating devices create a triple response on the skin which may be characterized by wheal, flare, and/or a sense of irritation created over regions of the head and neck during the prodromal stage of migraine. The devices thereby mitigate or even abort the painful headache associated with the migraine syndrome.

Use of an Implantable Self-Stimulation Implant Attached to Outer Bone Table For Automatic Stimulation of and Desensitization of The Trigeminal Nerve Using Natural Facial Movement During Facial Expression

[0092] In one embodiment, a method of stimulating the trigeminal nerve branches to achieve desensitization involves the use of an implant which tethers dermal and attached facial muscular elements to underlying bone. In one embodiment, the implant can be placed with a micro incision in the region of the scalp, forehead, brow, occipital area, face, posterior auricular region with the intention of attaching muscular and dermal elements to bone. During natural facial movements, alteration in the sensory nerves produced by this type of fixation can serve to desensitize the trigeminal nerve to provide for a spontaneous, constant effect not requiring self stimulation or any conscious effort by the patient treated for migraine or related headache disorders. With natural facial movement and facial expression, this type of tissue tethering has been shown to decrease photophobia, an important component of the migraine syndrome. The implant is fixated to bone and can be applied in regions not containing critical vessels and motor nerves to avoid complications of hemorrhage or paralysis. The effect will create an internal type of neurogenic inflammation mimicking the triple response of Lewis, involving stimulating and desensitizing the trigeminal nerve, so that this nerve would be less prone to contribute to sensitization in conjunction with central nervous system sensitization within the thalamus and related brain structures so that evolution of migraine pain is mitigated or aborted.

[0093] In one embodiment of a component of a method of migraine treatment, a 3-10 mm, preferably a 3-7 mm screw, and most preferably a 4-5 mm screw is placed in certain areas of the forehead, brow, face and scalp to provide dermal muscle fixation and stimulation of trigeminal nerve sensory elements using a tightly fixating wrench through 1-2 mm incisions impaling dermal elements, muscular elements and placing a tight fixation by compressing these elements firmly against underlying bone. In certain embodiments, the screw is titanium. Minimal closure effort is made with one or two sutures. During the healing process, the fixation creates an altered sensation and a sensory stimulus simulating self administered pressure or stimulation often applied by the patient who suffers from migraine or related headaches. [0094] One implementation is most useful in treating those afflicted with chronic recurrent headaches making intermittent self stimulation on the skin surface difficult and likely effective because of frequent applications. Migraine patients with frequent attacks often undergo central sensitization which can not easily be treated by self stimulation during the prodromal periods, so that a more robust method of stimulation requiring this fixation implant who be a preferred method of therapy. This application would be best applied in migraine with severe chronic daily headaches or severe forms of chronic myofascial headaches.

[0095] In certain embodiments, the screw and/or pin placement can be anywhere along the facial bone, but most preferably in the periorbital area. The pin can be placed at angles or variable depths to achieve maximal effect or sensory nerve stimulation. Pin placement in close proximity to the supra-orbital nerve gives maximal stimulating effect. Pins once surgically placed may be stimulated by external devices (for example, electrical or ultrasonic devices or their equivalents as is known in the art) to enhance effects on sensory nerve stimulation.

[0096] In certain embodiments, a method for treating chronic recurrent migraine or related headaches in a subject comprises surgically implanting a device through a micro incision in the subject's skin. The device causes a fixation of the subject's dermis and muscle elements to the subject's bone, which desensitizes the trigeminal nerve. In certain embodiments, a method for treating chronic severe tension or related headaches in a subject comprises surgically implanting a device through a micro incision in the subject's skin. In certain embodiments, a method for treating recurrent cluster headaches in a subject comprises surgically implanting a device through a micro incision in the subject's skin. In certain embodiments, a method for treating recurrent migraine and associated headaches in a subject comprises surgically implanting a device through a micro incision in the subject's skin. [0097] In certain preferred embodiments, the device comprises a metallic screw, and the method further involves compressing the subject's soft tissues to the subject's bone with engagement of the screw to the bone. In certain preferred embodiments, the metallic screw is titanium and measures between 4-5 mm. In certain preferred embodiments, the metallic screw is stainless steel. In certain preferred embodiments, the metallic screw is magnetic.

[0098] In certain preferred embodiments, the device is implanted in multiple locations.

[0099] In certain preferred embodiments, the related headaches are severe myofascial pain, cluster headaches, cervciogenic headaches, headaches associated with fibromyalgia, or tension headaches.

[00100] In certain preferred embodiments, the method involves application of ultrasonic or electronic energy to enhance stimulation of the trigeminal nerve.

[00101] In certain embodiments, the invention is directed to a method for treating photophobia in a subject by implanting a metallic device fixated to bone in proximity to the subject's facial sensory nerves.

Example 14:

[00102] A 54 year old woman underwent an implantation procedure of a peri-orbitial and brow pin for neurologic blepharospasm. She also suffered from chronic tension and occasional migraine headaches. She noted a sensory trick which suppressed her involuntary movements. She underwent a brow pinning procedure which fixated her forehead scalp to the underlying osseous bone. Her involuntary blepharospasm improved over subsequent months. Although she suffered a usual mild post procedure headache, she unexpectedly and surprisingly benefited from the decreased incidence of subsequent tension and migraine headaches. She further noted that her general light sensitivity was improved and her ability to sustain her employment without absence from headache pain was increased.

Use of ao Implantable Self-Stimulation Implant Not Attached to Ositer Bone Table For Automatic Stimulation of and Desensittzation of The Trigeminal Nerve Using Natural

Facial Movement Diaring Facial Expression

[00103] in other embodiments, an object is to provide sensory nerve stimulation from an implant placed in close proximity to sensory nerves which stimulates the nerves during natural human movement and therefore, suppresses central pain centers in the brainstem, spine, or related brain areas for the purpose of mitigating symptoms of chronic pain. The surgical implant in certain circumstances may not have to attach to the subject's bone, but rather be placed in close proximity to a sensory nerve which during the course of natural facial movement, creates a point of stimulation of the sensory nerve, which causes central desensitization of pain centers in the brainstem or other associated pain centers in the central nervous system. Such an application of the implant exploits natural facial or other human movement occurring during blinking, facial expression, chewing, breathing, or the like to stimulate the sensory nerves in order to create an enhanced sensory impulse into the central nervous system which has the effect of suppressing pain associated with headache syndromes.

[00104] These methods and devices are not limited to head and neck, but work on other body regions which are afflicted with pain associated with tactile suppression, such as rubbing pressing, messaging, or touching, for example, myofascial pain, fibromyalgia (diffuse or generalized), arthritis and arthralgias, and muscle spasm related pain.

[00105] In various embodiments, the implant can be metallic, for example titanium, gold, stainless steel or any other tissue inert alloy. Ceramic implants are possible so long as the materials can create a sensory stimulation during movement. The implant may be an absorbable substance to as to not require potential future removal. Such substances may include but not limited to nylon, catgut, absorbable cloth fiber, silk, poly-L-lactic acid, polyglycolic acid, polymethyl methacrylate, and the like.

[00106] in some embodiments, absorbable implants may cause a limited inflammatory response which can further enhance sensory nerve stimulation during natural facial movement. Any implant used for this purpose can be placed at any tissue plane in close proximity to sensory nerves. Sensory nerves on the face include the trigeminal nerve (all divisions), cervical nerves, sensory division of facial nerve, and sensory nerves of the mandibular bone. This approach is not limited to the face, head and neck.

[00107] In other embodiments, the implant is partially exteriorized so as to resemble a body piercing with a pin, ring, sphere, or any ornate metallic figure for aesthetic camouflage. Exteriorized implants also may further provide enhanced sensory stimulation because of proximity to superficial cutaneous nerve endings. An example of a none bone fixed implant for the treatment of chronic tension and chronic migraine is given in the example below.

[00108] Example I5

[00109] A 53 year old woman experienced blepharospasm and severe chronic migraine and chronic tension headaches (myofascial pain headaches and neck aches). She did not wish a bone fixed implant. A gold metallic brow ring, usually used for aesthetic appeal, was recommended and therefore placed through the brow in closure proximity to the supra-orbital nerve (first division of trigeminal nerve). She experienced marked improvement in the severity and frequency of her headache syndrome and coniued to wear the exteriorized soft tissue ring for several years. [00110] Table 1: Headaches With Which the Implantable Device May be Used (1988 Headache and Facial Palo Classification System by the International Headache Society; Classification of headache disorders, cranial neuralgias, and facial pain)

Migraine

1.1 Migraine without aura

1.2 Migraine with aura

1.2.1 Migraine with typica! aura

1.2.2 Migraine with prolonged aura

1.2.3 Familial hemiplegic migraine

1 .2.4 Basilar migraine

1.2.5 Migraine aura without headache

1.2.6 Migraine with acute onset aura

1.3 Ophthalmoplegic migraine

1.4 Retinal migraine

1.5 Childhood periodic syndromes that may be precursors

to or associated with migraine

1.5.1 Benign paroxysmal vertigo of childhood

1.5.2 Alternating hemiplegia of childhood

1 .6 Complications of migraine

1.6.1 Status migrainosus

1.6.2 Migrainous infarction

1 .7 Migrainous disorder not fulfilling above criteria . Tension-type headache

2.1 Episodic tension-type headache

2.1 .1 Episodic tension-type headache associated with disorder of pericranial muscles

2.1 .2 Episodic tension-type headache unassociated with disorder of pericranial muscles

2.2 Chronic tension-type headache

2.2.1 Chronic tension-type headache associated disorder of pericranial muscles

2.2.2 Chronic tension-type headache unassociated with disorder of pericranial muscles

2.3 Headache of the tension-type not fulfilling above criteria . Cluster headache and chronic paroxysmal hamlererarisa

3.1 Cluster headache

3.1.1 Cluster headache periodicity undetermined 3.1.2 Episodic duster headache

3.1 .3 Chronic cluster headache

3.1 .3.1 Unremitting from onset

3.1 .3.2 Evolved from episodic

3.2 Chronic paroxysmal hemicrania

3.3 Cluster headache-like disorder not fulfilling above criteria . Miscellaneous headaches unassociated with

structural lesion

4.1 Idiopathic stabbing headache

4.2 External compression headache

4.3 Cold stimulus headache

4.3.1 External application of a cold stimulus

4.3.2 Ingestion of a cold stimulus

4.4 Benign cough headache

4.5 Benign exertional headache

4.6 Headaches associated with sexual activity

4.6.1 Dull type

4.8.2 Explosive type

4.6.3 Postural type < Headache associated with head trauma

5.1 Acute posttraumatic headache

5.1.1 With significant head trauma and/or confirmatory signs

5.1.2 With minor head trauma and no confirmatory

signs

5.2 Chronic posttraumatic headache

5.2.1 With significant head trauma and/or confirmatory signs

5.2.2 With minor head trauma and no confirmatory signs . Headache associated with vascular disorders

6.1 Acute ischemic cerebrovascular disease

6.1.1 Transient ischemic attack (TIA)

6.1.2 Thromboembolic stroke

6.2 intracranial hematoma

6.2.1 Intracerebral hematoma

6.2.2 Subdural hematoma

6.2.3 Epidural hematoma

6.3 Subarachnoid hemorrhage

6.4 Unruptured vascular malformation

6.4.1 Arteriovenous malformation

6.4.2 Saccular aneurysm

6.5 Arteritis

6.5.1 Giant cell cell arteritis 8.5.2 Other systemic arteritides

6.5.3 Primary intracranial arteritis

6.8 Carotid or vertebral artery pain

6.6.1 Carotid or vertebral dissection

8.6.2 Carotidynia (idiopathic)

6.6.3 Post endarterectomy headache

6.7 Venous thrombosis

6.8 Arterial hypertension

6.8.1 Acute pressor response to exogenous agents

6.8.2 Pheochromocytoma

8.8.3 Malignant (accelerated) hypertension

6.8.4 Preeclampsia and eclampsia

6.9 Headache associated with other vascular dirorder , Headache associated with nonvascular intracranial disorder

7.1 High cerebrospinal fluid pressure

7.1.1 Benign intracranial hypertension

7.1.2 High-pressure hydrocephalus

7.2 Low cerebrospinal fluid pressure

7.2.1 Post lumbar puncture headache

7.2.2 Cerebrospinal fluid fistula headache

7.3 Intracranial infection

7.4 Intracranial sarcoidosis and other noninfectious inflammatory diseases

7.5 Headache related to intrathecal injections

7.5.1 Direct effect

7.5.2 Due to chemical meningitis

7.6 Intracranial neoplasm

7.7 Headache associated with other , Headache associated with substances or their withdrawal

8.1 Headache induced by acute substance use or exposure

8.1.1 Nitrate/nitrite induced headache

8.1.2 Monosodium giutamate induce

8.1.3 Carbon monoxide induced headache

8.1.4 Alcohol-induced headache

8.1.5 Other substances

8.2 Headache induced by chronic substance use or exposure

8.2.1 Ergotamine induced headache

8.2.2 Analgesics abuse headache

8.2.3 Other substances 8.3 Headache from substance withdrawal (acute

use)

8.3.1 Alcohol withdrawal headache (hangover)

8,3.2 Other substances

8.4 Headache from substance withdrawal (chronic use)

8.4.1 Ergotamine withdrawal headache

8.4.2 Caffeine withdrawal headache

8.4.3 Narcotics abstinence headache

8.4.4 Other substances

8.5 Headache associated with substances but with uncertain mechanism

8.5.1 Birth control pills or estrogens

8.5.2 Other substances

9. Headache associated with noncephalic infection

9.1 Viral infection

9.1.1 Foca! noncephalic

9.1.2 Systemic

9.2 Bacterial infection

9.2.1 Focal noncephalic

9.2.2 Systemic (septicemia)

9.3 Headache related to other infection

10. Headache associated with metabolic disorder

10.1 Hypoxia

10.1.1 High-altitude headache

10.1.2 Hypoxic headache (law-pressure environment, pulmonary disease causing hypoxia)

10.1.3 Sleep apnea headache

10.2 Hypercapnia

10.3 Mixed hypoxia and hypercapnia

10.4 Hypoglycemia

10.5 Dialysis

10,8 Headache related to other metabolic abnormality

11. Headache or facial pairs associated with disorder of cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or other facia! or cranial structures

1 1.1 Cranial bone

1 1.2 Neck

1 1.2.1 Cervical spine

1 1.2.2 Retropharyngeal tendinitis

1 1.3 Eyes

1.3.1 Acute glaucoma

1.3.2 Refractive errors

1 1.3.3 Heterophoria or heterotropia

1 1.4 Ears 1 1.5 Nose and Sinuses

1 1.5.1 Acute sinus headache

11.5.2 Other diseases of nose or sinuses

1 1.6 Teeth, jaws and related structures

1 1.7 Temporomandibular joint disease (functional disorders are coded to group

2) 12. Crania! neuralgias, nerve trunk pain, and deafferentatiort pain

12.1 Persistent (in contrast to tic-like) pain of cranial nerve origin

12.1.1 Compression or distortion of cranial nerves and second or third cervical roots

12.1.2 Demyelination of cranial nerves

12.1.2.1 Optic neuritis (retrobulbar neuritis)

12.1.3 Infarction of cranial nerves

121.3.1 Diabetic neuritis

12.1.4 Inflammation of cranial nerves

12.1.41. Herpes zoster

12.1.4.2 Chronic postherpetic neuralgia

12.1.5 Tolosa-Hunt syndrome

12.1.6 Neck-tongue syndrome

12.1.7 Other causes of persistent pain of cranial nerve origin

12.2 Trigeminal neuralgia

12.2.1 Idiopathic trigeminal neuralgia

12.2.2 Symptomatic trgeminal neuralgia

12.2.2.1 Compression of trigeminal root or ganglion

12.2.2.2 Central lesions

12.3 Glossopharyngeal neuralgia

12.3.1 Idiopathic glossopharyngeal neuralgia

12.3.2 Symptomatic glossopharyngeal neuralgia

12.4 Nervus intermedius neuralgia

12.5 Superior laryngeal neuralgia

12.8 Occipital neuralgia

12.7 Central causes of head and facial pain other than tic douloureux

12.7.1 Anaesthesia dolorosa

12.7.2 Thalamic pain

12.8 Facia! pain not fulfilling criteria in groups 1 1 and 12 . Headache not classifiable

[00111] The patent applications and other literature referred to in the instant specification are incorporated herein by reference in their entireties. The description of the embodiments, examples, and figures herein are given by way of example, and not by way of limitation. A ordinary skill in the relevant art is a medical doctor.