New research on how Botox relieves chronic migraines and how to predict who will respond to Botox

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.

  1. Dr. Mauskop says: 01/19/20169:46 am

    No, there is no increase in side effects with more frequent injections of Botox. Many of my patients require injections every 10 weeks and a handful needs them every 8-9 weeks. There is no difference in response to Botox between women and men.
    Regarding venlafaxine, you should be aware that it often takes 150 mg for it to have pain relieving effect because that is the dose that triggers serotonin and epinephrine activity. At lower doses venlafaxine acts just like selective serotonin reuptake inhibitors, such as fluoxetine (Prozac), which do not relieve migraines or pain. Another thing to keep in mind is that venlafaxine should be stopped very gradually because it often causes withdrawal symptoms, such as severe anxiety.

  2. Adam says: 01/19/20168:38 am

    Hi Dr. Mauskop. I am 25 years old, had migraines since I was 9, thought I outgrew it in my early 20’s, but sadly they came back a year and a half ago and transformed quickly to chronic migraine. I am about to have my 4th round of Botox (10 weeks instead of 12 this time) and I am cautiously optimistic that I may be transforming back to episodic. My daily migraine/headache has improved, and I have recently experienced a reduction of migraines to only one-two times a week (although my migraines require 2 doses of Triptans and a next day hangover from triptans). I also recently started 37.5mg Venlafaxine as well (hopefully temporary-dont want to stay on SNRI too long).
    My question is about the Botox- Do you find there are any increased side effects with Botox every 10 weeks (instead of every 12)? Also, do you notice a difference in how males respond to Botox as opposed to women migrainuers?
    Thank you for all you do to help the migraine community!

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