Migraine Treatment of the Month: BotoxA
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Although onabotulinumtoxinA (BotoxA) has been FDA-approved for the treatment of chronic migraine for well over 10 years, it still comes as a surprise to many patients plagued by persistent and often disabling headache that the same BotoxA used to flatten wrinkles also may flatten migraine.
To an interesting extent, the history of this neurotoxin’s evolution as a headache therapy has paralleled our evolving knowledge of migraine and the biology that underlies the disorder. When BotoxA first was evaluated on a wide scale basis for its potential effectiveness in managing headache, the headache disorder chosen for study was chronic tension-type headache (CTTH). At that time it was thought that CTTH resulted from involuntary, subconscious and chronic contraction of face, head, neck and shoulder musculature and that this unnatural contraction of muscle was generating headache. It consequently seemed reasonable to hypothesize that relaxing the involved muscles would reduce headache. It didn’t. Evidence has emerged to suggest that individuals afflicted by CTTH are no more likely to exhibit sustained muscle contraction then those free of the disorder. It is no exaggeration to say that at this point no one has a clear idea as to what causes CTTH…much less how to treat it.
Over the years, and not unlike the development of an urban legend, one began to hear reports of patients with migraine receiving Botox for cosmetic reasons and unexpectedly experiencing a reduction in their migraine burden. Along with this, it was found that when Botox was injected into the muscles causing cervical dystonia, a forced deviation of the head and neck laterally in one direction or backwards, the pain associated with that involuntary deviation began to lessen even before the dystonia improved. In other words, Botox appear to have what is termed an antinociceptive effect . Put in simple terms, Botox appeared to have the potential for directly reducing pain without the intermediate step of relaxing muscle.
This led to a large scale studies involving Botox administered to patients with episodic migraine, but for whatever reason those studies failed to establish the neurotoxin’s effectiveness in that patient population. Staying the course, investigators then turned to chronic migraine and for that common variant of migraine Botox clearly exerted a therapeutic affect. For the first time there existed for the millions of Americans with chronic migraine a treatment specifically indicated for their headache disorder.
There are now other evidence-based therapies for preventing/suppressing chronic migraine (see So What Else is New? in this issue), but serial Botox injection therapy still remains an attractive option for patients with chronic migraine. Botox therapy has been with us for a long time and in use for multiple medical indications, and its safety record is excellent. Side effects are rare. Performed by an experienced injector, the 31 (yes, 31) intramuscular injections into the forehead, temples, back of the head, neck and shoulders which are administered every 12 weeks can be performed rapidly and with minimal discomfort. About the only side effect encountered these days is potential drooping of the eyelid, and this occurs infrequently and invariably resolves over a period of weeks.
How does migraine work to suppress chronic migraine? At the “downstream” end of migraine’s biologic circuit, the trigeminal nerve releases a chemical neurotransmitter, calcitonin gene-related peptide (CGRP). The CGRP then docks with a receptor on a nearby blood vessel to initiate the cascade of molecular events that result in migraine headache. One leading hypothesis for BotoxA’s mechanism of action is that it blocks a nerve cell protein that otherwise would transport CGRP to the position where it could be released from the nerve ending. In short, the bullet (CGRP) never makes its way to the chamber from which it would be fired at the target (head pain receptor located on blood vessel). By doing so, BotoxA reduces the activity of the migraine circuit like a rheostat dimming down a light.
Many patients begin begin to notice a meaningful reduction in headache burden within the first few weeks following their initial set of injections, and with continued treatment a reasonably high percentage of patients will become headache-free or nearly so, improving to the point that they can stop treatment and subsequently experience no worsening of their headache disorder for months and even years.
Physicians who can recall the sense of futility experienced in attempting to treat chronic migraine with medications possessed of no scientific evidence basis look back on 2010 and the emergence of BotoxA fondly. In its own way, BotoxA ignited a revolution in the science and treatment of chronic migraine just as injectable sumatriptan launched the migraine revolution 18 years before.
