Information for families

Onabotulinum toxin A is a medication which can be used to treat chronic migraine, meaning headache at least 15 days/month for at least 3 months, sometimes accompanied by migraine features like nausea or sensitivity to light and sound. It is injected in small amounts over several places on the face, head, neck, and shoulders. It is approved by the FDA for use in adults, but is also used “off-label” in teens. We don’t know exactly how onabotulinum toxin works to prevent headaches. One possibility is that the medicine works by tracking back through the nerves that carry pain messages to turn off pain signals in the brainstem. Since the onabotulinum toxin works near the site of injection, it does not usually cause side effects like sleepiness, thinking problems, or mood changes.

To use onabotulinum toxin A, your headache specialist will inject a very small amount of medicine into 30 or more spots. These will be spread over the forehead, sides of the head, back of the head, neck, and shoulders. The benefits can start 1 week after injections, and usually last until about 10–12 weeks after the injections. The injections are repeated every 12 weeks until headaches are well-controlled. If the onabotulinum toxin does not help on the first try, it is usually recommended to repeat the injections once 12 weeks later. Some patients who were not helped the first time do see benefit after repeated injections.

Side effects are generally mild. Some people are very anxious about the injections; it will be important to discuss this with your doctor. There is usually minimal discomfort associated with the injections, but if the headache is severe the injections may feel more painful. This initial discomfort lasts just a few minutes. Some patients will experience a worsening of head and neck pain for the first few days after the injections. To prevent this, your child may use ice and an anti-inflammatory medication such as ibuprofen or naproxen for a few days after the procedure and should avoid carrying a backpack until the neck/shoulder pain is resolved. Many patients find that their forehead muscles don’t move while the medicine is active. Other side effects can include droopy eyelid and weakness of chewing muscles or neck muscles, which is rare when the medication is administered by an experienced injector. Even when present, these side effects are usually mild, and wear off when the medication wears off at 12 weeks. Any injection carries a small risk of bleeding or infection. There have been rare cases of more serious breathing or swallowing problems when onabotulinum toxin A was used for tight muscles or salivary problems in children with cerebral palsy.

Some insurance companies will cover onabotulinum toxin A medicine and injections for children or teens. They usually require a diagnosis of chronic migraine, and documentation that the child has not had much benefit from at least 2 or 3 classes of preventive prescription medications. Some insurance companies will not cover it for patients under 18 years at all. If it is covered, two authorizations are needed in the United States. The insurance company has to authorize the procedure to inject the medicine. The insurance company’s specialty pharmacy has to approve the medicine. It can take weeks to obtain these authorizations. The portion of the total treatment cost which must be paid by the family depends on the details of the insurance plan.

Information for primary care clinicians

Onabotulinum Toxin A is approved for the preventive treatment of chronic migraine in adults aged > 18. It is used “off-label” in pediatric chronic migraine, as well as in other chronic headaches that can have overlapping symptoms with migraine including new daily persistent headache (NDPH) and persistent headache attributed to traumatic head injury, which is often referred to as post-traumatic headache. It is not entirely clear how onabotulinum toxin works to help prevent headaches. One hypothesis is that onabotulinum toxin helps to disrupt nerve signaling in the pain pathways in the peripheral trigeminovascular neurons, which are implicated in the initiation of a migraine. The largest trial evaluating onabotulinum toxin for headache was the PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) trial, which included only adults with chronic migraine. Onabotulinum toxin was found to be well-tolerated and effective, with a significant reduction in both headache frequency and severity. In this trial, 155 units of onabotulinum toxin were delivered as a series of 31 intramuscular injections over predefined points on the face, scalp, neck, and upper back. Injections were repeated on a 12-weekly cycle.

The evidence for onabotulinum toxin in the treatment of migraine in children and adolescents is more limited. Several pediatric studies, mostly case series, have described benefit with the use of onabotulinum toxin injections for children with medically-intractable migraine and daily headache. Randomized-controlled data has been mixed. Pediatric headache specialists may recommend onabotulinum toxin injections as a preventive treatment for children and adolescents with chronic migraine after other natural, integrative, and oral preventive therapies have been trialed without success. Most headache specialists will follow the adult PREEMPT dosing and injection protocol in adolescents and teens being treated with onabotulinum toxin.

Information for headache specialists

Onabotulinum toxin A is a neurotoxin derived from Clostridium botulinum, which has been a well-established therapeutic intervention for a wide variety of FDA-approved indications including the treatment of cervical dystonia, spasticity, blepharospasm, and neurogenic bladder, among others. Open-label studies have described long-term tolerability as well as benefit in adults with chronic migraine with and without daily headache, with and without allodynia, and in those with new daily persistent headache and persistent post-traumatic headache. The exact mechanism of onabotulinum toxin in modulating headache pain is unknown. The primary hypothesis is that onabotulinum toxin inhibits nociception in peripheral trigeminovascular neurons. Trigeminal and meningeal nociceptors are implicated in the initiation of a migraine via fusion of mechanosensitive ion channels in the nerve terminal membrane, and onabotulinum toxin may exert a preventive benefit by preventing the fusion of these channels.

The PREEMPT trial, which included only adults with chronic migraine, demonstrated a 50% or better reduction in total headaches days per month by the second injection cycle in about half of the patients included. The injections as per PREEMPT are repeated on a 12-weekly cycle. Some patients may be quicker metabolizers of the onabotulinum toxin and begin to notice “wear-off” effect earlier. In these patients, consideration may be given towards moving up the injection cycles by no less than 10-week intervals.

The PREEMPT protocol divides the head/neck into seven specific regions: procerus (5 units over 1 site); corrugator (10 units over 2 sites); frontalis (20 units over 4 sites); temporalis (40 units over 8 sites, 4 on each side); occipitalis (30 units over 6 sites, 3 on each side); the cervical paraspinal muscles (20 units over 4 sites, 2 on each side); and the trapezii (30 units over 6 sites, 3 on each side). As a point of practicality, given that onabotulinum toxin vials come in units of 50, in order to provide the standard 155 unit dose, a 200-unit vial would have to be used. With these additional units, neurologists have considered the option of increasing the dose at certain injection sites or adding additional injection sites based on the individual’s specific pain pattern, as elicited by myofascial pain via palpation of the head/neck regions. This has become known as the follow-the-pain protocol, which many clinicians now use in adjunct to the standard PREEMPT protocol.

Several pediatric case series have described benefit with the use of onabotulinum toxin injections for children with medically-intractable migraine and daily headache. One parallel-design randomized trial of a single treatment of onabotulinum toxin 155 units versus 74 units versus placebo in adolescents with chronic migraine did not demonstrate benefit of onabotulinum toxin over placebo injections. However, parallel-design randomized trials of therapies for migraine in children are known to have high rates of placebo response, making it difficult to demonstrate efficacy of active therapy over placebo. A more recent double-blinded placebo-controlled trial compared onabotulinum toxin 155 units to placebo over a 48-week period in adolescents with chronic migraine. Study results supported tolerability and efficacy for onabotulinum, with decreased headache frequency, severity, and function-related disability scores. Given the possible benefit suggested in limited pediatric trials, and the established benefit and safety in adults, many pediatric headache specialists use onabotulinum toxin injections as a preventive treatment for children and adolescents with chronic migraine. This therapy is typically considered when there has not been sufficient benefit achieved despite therapeutic treatment trials of multiple preventives including oral prescription medications and/or cognitive behavioral therapy.

Injection training materials are available at headache and neurology conferences, and through the company that makes the toxin.

Information for families

A peripheral nerve block is a procedure that uses local anesthetic (numbing) medicines to block messages coming from sensory nerves. Nerve blocks have been shown to help adults with several different types of headaches. In children and teens, nerve blocks can help with migraine, headache after concussion, and new daily persistent headache.

Numbing medicines (like lidocaine and/or bupivacaine) are injected with a very small needle. It is very similar to the injection that a dentist uses to numb the mouth before filling a cavity. Injections are done over the nerves that control sensation in the area that hurts. For example, if pain is on one side at the back of the head then 1 or 2 injections will probably control that pain. Sometimes injections on the side or front of the head are done as well.

Think of a computer that glitches. Often turning it off, waiting, and turning it back on again can help get things back to normal. Think of your nerves in the same way. At first, these anesthetics block sensation, so there will be numbness together with decreased pain. The numbness only lasts for a few hours before sensation is restored. However, that brief break in nerve transmission may allow the pain nerve an opportunity to reset. The goal is that the pain relief will last much longer than the numbness, sometimes many days or even a few weeks.

A peripheral nerve block procedure is often performed in a regular examination room, and usually takes only a few minutes. There may be some discomfort when the medication is first injected, which feels like a brief pressure or pulling sensation (like tugging on the hairs at the base of your scalp for a few seconds). The medication may cause a temporary bump until it is absorbed by the skin and may cause redness. These usually goes away after a few minutes but for some can last for hours. Some people report that their head feels “spacey” or that they feel nauseated while their head feels numb. Some people become very anxious about the procedure. Anxiety can make the headache more severe, and rarely can cause fainting. Among those people whose pain returns within a few days, some report that the pain feels more severe. There are low risks of itching, rash, allergic reaction, and bleeding. There are very low risks of infection and damage to the nerves.

In certain cases, your headache specialist may consider a different type of nerve block, called a sphenopalatine ganglion (SPG) block. The SPG is a collection of nerve cells located just behind the bones of the nose on either side. This ganglion has a close relationship to the trigeminal nerve, which is one of the main nerve networks involved in headache. The SPG contains both sensory and autonomic nerve fibers. Autonomic nerves are specialized nerves involved in controlling the automatic parts of our body’s function, such as heart rate and blood pressure. In the SPG, the autonomic nerve fibers help regulate tears in the eyes and congestion in the nose.

The SPG has connections to the brainstem, which is where the signals for many types of headaches are generated. The SPG also has connections to the pain-sensitive tissues covering the brain, via the trigeminal nerve. When your brain is making a headache, pain receptors are activated in the brainstem which send signals through the trigeminal nerve. These signals eventually make their way to the sensory area of the brain and let your brain know you are having pain. In migraine and cluster headache, nerves carrying these pain signals pass through the SPG. This is why, with these types of headaches, there can sometimes be symptoms such as eye tearing or nasal congestion.

The clinician may use a cotton swab or a device called a catheter to perform the SPG block. The catheter technique involves placing a very thin plastic tube into the nose to insert numbing medication in and around the SPG. During the procedure, there may be mild pressure and you may feel like sneezing. Some patients also experience a quick burning sensation or have a bad taste in the mouth. Sucking on a piece of candy during the procedure can help provide a distraction taste. Tearing and a brief temperature change may occur on the side of the nostril where the medication has been applied. For some, there is an immediate reduction in head and/or facial pain, but results can take anywhere from 15 min to a few hours to occur. The risks of the procedure are typically minimal. They include discomfort during and after the procedure, numb sensation in the back of the throat if any medication drips down, bitter taste, bleeding from the nose, and light-headedness. These side effects are typically mild and resolve within minutes to a few hours.

Information for primary care clinicians

Peripheral nerve blocks are an interventional procedure in which local anesthetic medication (typically lidocaine, bupivacaine, or a combination of the two) is injected over branches of the occipital and trigeminal nerves. The medication infiltrates the soft tissue and is taken up by the nerve endings, effectively anesthetizing the nerve territory. While this period of anesthesia is relatively short-lived ( usually 2–6 h, depending on the anesthetic used and individual metabolism ), the analgesic effect can be more sustained.

Similar to restarting a computer, anesthetizing the nerves perpetuating the headache pain forces them to reboot. Forcing the nerves to briefly “turn off” allows for the interruption of nociception, thereby disrupting pain processing through the network, and providing an opportunity for the nerves to reset their signaling frequency. This is why the benefit for pain reduction continues even after the medication wears off and the nerves come back online.

There are several nerves involved in processing headache pain that can be targeted with nerve block injections, including the greater and lesser occipital nerves, the auriculotemporal nerves, and the supratrochlear and supraorbital nerves. The occipital nerves are the most commonly targeted for peripheral nerve blocks. The occipital nerves communicate with the other nerves of the head and neck through the pain relay center in the brainstem, the trigeminal nucleus caudalis (TNC). Think of the occipital nerves as the “on-ramp” to the pain signaling highway, and the pain signaling as traffic. If you can block the on-ramp, you can interrupt the traffic.

Given the broad mechanism of action, nerve blocks can be considered for a number of different headaches. Retrospective, uncontrolled pediatric case series have described benefit from nerve blocks as both acute and preventive treatment for migraine, including chronic migraine, and post-traumatic headache, as well as for new daily persistent headache (NDPH). Occipital nerve blocks are also used for cluster headache, hemicrania continua, occipital neuralgia, and cervicogenic headache —although these conditions are far less common in pediatrics. In the presence of myofascial pain, trigger point injections (TPIs) may be considered alongside peripheral nerve blocks. The presence of active trigger points, in both primary and secondary headaches, may be associated with greater intensity and longer duration of headache. Although the exact mechanism is unknown, trigger points may be formed in part as a result of abnormal endplate potentials leading to excessive acetylcholine release in the neuromuscular junction, resulting in the formation of a taut band.

Another target for possible nerve blockade is the sphenopalatine ganglion (SPG). Also called the pterygopalatine ganglion, the SPG is an extra-cranial parasympathetic ganglion found in the pterygopalatine fossa posterior to the middle nasal turbinate. The ganglion has both sensory and autonomic (sympathetic and parasympathetic) components. The autonomic pathway is activated during many different types of headaches including migraine. This activation may manifest with a variety of symptoms including lacrimation, nasal congestion, rhinorrhea, forehead/facial sweating, conjunctival injection, nausea, emesis, diarrhea, and polyuria. Clinical trials have supported the efficacy and tolerability of SPG blocks for both acute and chronic migraine in adults. SPG blocks have also been evaluated for the treatment of other primary and secondary headaches, including the trigeminal autonomic cephalalgias (cluster headache, paroxysmal hemicrania); trigeminal neuralgia; atypical facial pain; and headache attributed to temporomandibular joint disorder.

Information for headache specialists

The indications for nerve blocks are reviewed above in the primary care clinician’s section. Our own retrospective study of nerve blocks, in which injections were tailored to the individual response of teenagers with headaches unresponsive to prior treatments, found that 86% of those with acute headache flare had at least transient improvement in pain severity. Despite the lack of controlled trials, nerve blocks and trigger point injections are used commonly among pediatric headache specialists. A survey of the Pediatric & Adolescent Section of the American Headache Society (AHS) found that 80% of respondents either perform or refer patients for peripheral nerve blocks. There is wide variability in the medication used, site(s) injected, and in the use of repeated injections. Additional information regarding injection methodology and recommended technique is available for interested clinicians, based on expert consensus review.

The indications for SPG blocks are reviewed above in the primary care clinician’s section. As an acute intervention, SPG blocks may block sensory afferent sensory fibers projecting to the trigeminal nucleus caudalis (TNC). As a preventive intervention, repeated SPG blocks may disrupt the autonomic pain cycle, reducing pain over time by changing processing through the TNC via afferent blockage of the SPG. Clinical trials have supported the efficacy and tolerability of SPG blocks for both acute and chronic migraine in adults. As a preventive treatment, SPG blocks can be performed twice a week over 6 weeks period.

The traditional transnasal topical approach for SPG blocks involves using a cotton tipped applicator soaked in lidocaine, applied posteriorly to the middle nasal turbinate on the nasopharyngeal mucosa. More recently, transnasal devices have recently been made available for administration to accommodate varying anatomy and ensures that the anesthetic more reliably reaches the ganglion. These devices are minimally invasive and the procedure can be performed as quickly as 10 s on each side.

The three devices currently FDA-cleared and commercially available are the SphenoCath ( Dolor Technologies, Salt Lake City, UT ); Allevio SPG Nerve Block Catheter ( Jet Medical, Schwenksville, PA ); and the Tx360 ( Tian Medical, Lombard, Il, USA ). Studies comparing the efficacy of all the three devices are lacking.

In pediatrics, SPG blocks have been studied for the acute treatment of migraine. A retrospective review of a total of 489 SPG blocks performed in patients aged 6 to 26 years with migraine or status migrainosus demonstrated complete technical success for all procedures, and a significant reduction in pain scores. No immediate or acute complications were reported. SPG blocks appear to be a safe and relatively minimally-invasive treatment approach. Although further pediatric studies are needed, SPG blocks may be a viable treatment approach in refractory headache, as an alternative to the need for IV medication, hospital admission, or prolonged use of oral pain medication with risk of medication overuse headache.