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Thread: anti-CGRP meds for flushing

  1. #1
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    Default anti-CGRP meds for flushing

    Recently, anti-CGRP drugs like Emgality, Ajovy, and Aimovig have become available in the US for migraine (not sure about other countries). There is evidence that CGRP (potent vasodilator) may play a role in flushing and menopausal flushing. It is released by the peripheral sensory nerves in the context of many different conditions involving neurogenic inflammation including CRPS, arthritis, fibromyalgia, and migraine. I believe that evening flushing is also a manifestation of neurogenic inflammation. My evening flushing has only been helped by botox (which blocks neurogenic inflammation and thus CGRP / substance P release from the nerves), and recently Aimovig (my evening flushing has also been helped by nerve membrane stabilizers like lidocaine, but they have proved tricky to get right). The caveat I have though, is that if your evening flushing is actually a rebound from being "too cold" at some point during the day (and this may not be obvious) -- it might increase pain while at the same time inhibiting the reactive flushing (I think, but am not sure, that the reactive Raynaud's flushing involves CGRP release from the nerves). Still, learning that might be helpful (in that case may benefit from dilators like aspirin/magnesium taken in the afternoon).

    Other meds I have tried like clonidine, beta blockers -- my instinct is that these guys never addressed the pathophysiological mechanism what was going on, because it was never clear that they were helpful for me (I'd just be "too cold" in between flushings). They do not address neurogenic inflammation at all.

    "The opposite condition to that seen in Raynaud’s
    disease, an increase in CGRP release, is believed to be
    involved in the onset of blushing syndromes. Estrogen
    levels are decreased (leading to a relative increase in
    androgens) in peri- and postmenopausal women, who
    commonly suffer from uncomfortable and embarrassing hot flushes and episodic sweating. These can be
    alleviated by hormone replacement therapy (225). The
    flushing is believed to be due to an increase in release
    of CGRP, which is found to be elevated in serum and
    urine during attacks, although the tachykinins which
    colocalize with CGRP are not found to increase (53,
    389). A similar condition is seen in males with a loss in
    circulating androgens, after surgical removal of the
    prostate gland in prostate cancer. In this case, it seems
    to be the relative increase in estrogens that leads to hot
    flushes, where again an increase in plasma CGRP is
    observed (329). These studies suggest that sex hormone levels are linked to the production/release of
    CGRP, although the precise mechanisms remain to be
    determined. ...

    One of the major advances in recent years has been
    the synthesis of nonpeptide molecules that are capable
    of antagonizing effects mediated via the CGRP receptor. Indeed, as discussed in sections IV and IX, there is
    currently a compound in clinical trials for migraine
    therapy. There is compelling evidence for a role for
    CGRP in the pathology of migraine, and the results of
    these trials are eagerly awaited. However, in keeping
    with all other new drugs, a lack of side effects is
    essential. Thus an essential component in the drug
    development is a requirement to prove that the CGRP
    antagonist is not instrumental in producing/worsening
    other illnesses, such as Raynaud’s syndrome, pulmonary hypertension, ischemia/reperfusion injury, or congestive heart failure as a result of decreased CGRP
    activity. Interestingly, other possible outcomes such as
    inhibition of facial flushing may be considered an advantage, rather than a disadvantage of the drug.
    "

    https://www.physiology.org/doi/pdf/1...rev.00037.2003


    "The regulation of CGRP synthesis is still poorly understood. CGRP synthesis is known to be upregulated in models of nerve damage, such as peripheral axotomy, and it is thought that synthesis of the peptide is enhanced in tissues that are undergoing an inflammatory response " (I have been found to have small fiber neuropathy, as probable cause of my flushing/burning)

    "It is thought that inappropriate CGRP release is key to the facial reddening in blushing syndromes; postmenopausal women with facial flushing have elevated CGRP plasma levels compared with premenopausal women (157, 168, 438). There are also flushing episodes associated with medullary thyroid carcinoma, and this is possibly related to the raised CGRP plasma concentrations found in these patients "

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187032/

    Clear overview on how these anti-CGRP meds work in context of migraine (stabilizing mast cells, interrupting pain transmission, decreasing neurogenic inflammation) - https://www.biohavenpharma.com/scien...-role-migraine

    I think this might help many people. I do have to add in amlodipine (a dilator) personally so Aimovig does not trigger my Raynaud's burning. But it seems to take away the "oomph" of evening flushing for me. My ears are also dramatically less sensitive to touch.

    edit - insurance will probably only approve with diagnosis of chronic migraine and with doctor saying you "failed" ~2 standard chronic migraine meds like propranolol and topamax. There was a relatively high copay but Aimovig has assistance programs.

    Aimovig copay program link:
    https://www.aimovighcp.com/-/media/p..._brochure.ashx
    Last edited by laser_cat; 1st February 2019 at 09:56 PM.

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    Thanks for the info. This sounds very promising! How long have you been on it and what side effects are you experiencing? How much has it knocked down the flushing?

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    Aimovig/erenumab is now licensed for use in the UK, but is not available on the NHS yet. However, I suspect there are a limited number of private neurologists/headache experts now prescribing it.

    I'd be interested if anyone has tried it in the UK and their experience of it? I've found benefit with botox, and erenumab is supposed to be better than botox (that is the experience of people who actually took it in the trials for headaches), although the NHS/NICE will not concede to this point - yet!

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    Quote Originally Posted by sg321 View Post
    Thanks for the info. This sounds very promising! How long have you been on it and what side effects are you experiencing? How much has it knocked down the flushing?
    This

    Laser_cat how have you been getting on with it, would you recommend it based on your progress?

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    Senior Member laser_cat's Avatar
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    Sorry for the delay. The single dose (monthly injection) helped with flushing for about 1-2 wks, however sometimes I felt I was burning because my blood vessels were overly constricted. So I did have to add in a tiny bit of vasodilator for that. To me, botox works better - perhaps a more focused way to really block all nerves around in a specific area (blocking dilation from neurogenic inflammation from sensory nerves, blocking norepinephrine release from sympathetic nerves, and blocking acetylcholine, which is a vasodilator). In comparison, Aimovig blocks CGRP from sensory nerves (but not substance P, or other neurotransmitters in the neurogenic inflammation "soup").

    I think this might be ok for vascular rosacea without Raynaud's but probably not for the neurogenic rosacea / facial erythromelalgia that I have. It is nothing compared to the heat tolerance I get from lidocaine iv for example - so am likely going to stop Aimovig to focus more on pain / regular lidocaine iv's

    Note some people do a double dose (1 injection every 2 wks) in case a single dose doesn't carry them completely to the next month (for their migraines).

    Several anti-CGRP groups on facebook - side effects are still being reported but seem to include fatigue, constipation, hair loss. I had some fatigue

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    Quote Originally Posted by laser_cat View Post
    Sorry for the delay. The single dose (monthly injection) helped with flushing for about 1-2 wks, however sometimes I felt I was burning because my blood vessels were overly constricted. So I did have to add in a tiny bit of vasodilator for that. To me, botox works better - perhaps a more focused way to really block all nerves around in a specific area (blocking dilation from neurogenic inflammation from sensory nerves, blocking norepinephrine release from sympathetic nerves, and blocking acetylcholine, which is a vasodilator). In comparison, Aimovig blocks CGRP from sensory nerves (but not substance P, or other neurotransmitters in the neurogenic inflammation "soup").

    I think this might be ok for vascular rosacea without Raynaud's but probably not for the neurogenic rosacea / facial erythromelalgia that I have. It is nothing compared to the heat tolerance I get from lidocaine iv for example - so am likely going to stop Aimovig to focus more on pain / regular lidocaine iv's

    Note some people do a double dose (1 injection every 2 wks) in case a single dose doesn't carry them completely to the next month (for their migraines).

    Several anti-CGRP groups on facebook - side effects are still being reported but seem to include fatigue, constipation, hair loss. I had some fatigue
    Thanks so much for the detailed info, sorry to hear it wasn’t ideal for you, it still sounds like it could be a pretty useful additional treatment for the right candidates.

    Regarding botox, do you know if this can safely be done whilst also undergoing a course of IPL / v-beam?

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    Senior Member laser_cat's Avatar
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    Quote Originally Posted by Brooks View Post

    Regarding botox, do you know if this can safely be done whilst also undergoing a course of IPL / v-beam?
    I was told this would be fine, just would need to space out treatments (eg, takes a few days to recover from botox).

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