While Botox (OnabotulinumtoxinA) has been shown to be effective in treating chronic migraines, its exact mechanism of action is not clear. Initially, we thought that it works by relaxing muscles in the forehead, temples and the back of the head and neck. However, this is not likely for several reasons. One reason is that some people have pain at the top of their heads, where there are no muscle, and injecting those areas leads relief of pain. Another reason is that Botox seems to be effective in relieving different nerve pains, such as that of shingles (post-herpetic neuralgia), trigeminal neuralgia, and other.
Botox blocks the release of acetylcholine, a neurotrasmitter that is normally released into the space between the nerve ending and the muscle (synapse), making the muscle contract. We also know that Botox blocks the release of other neurotransmitters, which may be responsible for its pain-relieving properties. One of these chemical messengers is CGRP (calcitonin gene-related peptide).
A study just published in the journal Pain by Spanish researchers showed that CGRP level is increased in blood of patients with chronic migraine even when they are not having a migraine attack. CGRP levels were determined in 83 patients with chronic migraines (average age 44 years; 94% females) before and 1 month after treatment with 155 to 195 units of Botox. CGRP levels after Botox treatment were significantly lower as compared with CGRP levels obtained before Botox treatment. Pretreatment CGRP levels in responders were significantly higher than those seen in nonresponders. One month after treatment, the CGRP levels did not change in nonresponders, but significantly decreased in responders. Demographic factors, clinical features, and comorbidities (co-existing medical conditions) were not different in responders as compared with those of nonresponders. The authors concluded that “These results confirmed that CGRP levels can be of help in predicting the response to Botox and suggest that the mechanism of action of Botox in chronic migraine is the reversal of sensitization as a result of the inhibition of CGRP release.”
Unfortunately, the test to measure CGRP levels is not yet available outside research laboratories and because this was a small study we do not know how accurate this test will be. It has to tells us with greater than 90% which migraine sufferer will respond. If it is less than 90% accurate, we’d be denying over 10% of patients a very effective and often life-altering treatment. Some studies also suggested that we can predict who will respond and who will not by the description of pain. That is, if the pain is squeezing, crushing from outside in, or involves the eye, then the chances of response are better than if the pain is exploding, or from inside out. The accuracy of this predictor is less than 70%, so it should not be used to screen for potential non-responders.
