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Thread: Trigeminal sensory malfunction theory on the cause of rosacea

  1. #11
    Senior Member Brady Barrows's Avatar
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    Quote Originally Posted by babadah View Post
    Thanks Brady. After first quick reading, my impressions : when you google TRPV4 and inflammation, many other diseases come in results. So it's more like "something that participates in inflammation in other areas, does that in rosacea too" . The trigeminal nerve involvement looks unclear, it is associated to rosacea but they are not even sure what came first ( am i right on that ? )
    What does sound interesting is that an administration of a toxin blocked mast cell degranulation. Maybe that could bring another topical (in what, 10 years from here ?) Then again, another topical, another rebound effect concerns..
    If someone could explain what the abstract below means in laymen's terms, that would be helpful:

    "Mascarenhas et al. report that TRPV4 expression is upregulated in mast cells in response to the proteolytic cathelicidin fragment LL37 in a murine rosacea model and that TRPV4 loss of function attenuates mast cell degranulation. These findings render TRPV4 a translational-medical target in rosacea. However, signaling mechanisms causing increased expression of TRPV4 await elucidation. Moreover, we ask whether TRPV4-mediated Ca++-influx evokes mast cell degranulation."
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    Quote Originally Posted by Brady Barrows View Post
    If someone could explain what the abstract below means in laymen's terms, that would be helpful:

    "Mascarenhas et al. report that TRPV4 expression is upregulated in mast cells in response to the proteolytic cathelicidin fragment LL37 in a murine rosacea model and that TRPV4 loss of function attenuates mast cell degranulation. These findings render TRPV4 a translational-medical target in rosacea. However, signaling mechanisms causing increased expression of TRPV4 await elucidation. Moreover, we ask whether TRPV4-mediated Ca++-influx evokes mast cell degranulation."
    I would say, in summary, there is an over presence of TRPV4 - receptors/Calcium channels in rosacea skin mast cells. When they are blocked mast cells degranulate less - so less inflammation. So there is a possibility of developing a medication acting on these receptors - channels.
    A more educated explanation is welcome

  3. #13
    Senior Member Brady Barrows's Avatar
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    Quote Originally Posted by babadah View Post
    I would say, in summary, there is an over presence of TRPV4 - receptors/Calcium channels in rosacea skin mast cells. When they are blocked mast cells degranulate less - so less inflammation. So there is a possibility of developing a medication acting on these receptors - channels.
    A more educated explanation is welcome
    Thanks for your input. I have been receiving some explanations from the RRDi MAC members in this thread if you scroll down and read the comments.
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    Default Burning stinging pain

    Has anyone on this forum ever recovered from this ?

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    Senior Member Brady Barrows's Avatar
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    Quote Originally Posted by Losinghope View Post
    Has anyone on this forum ever recovered from this ?
    Yes, I did a search in the top right corner using your terms, 'burning stinging pain' and got lots of results. The first one on the list is an example:

    Nobrakes, post no 5, says, "Have you tried a urea cream? It's been a revelation for me. I don't want to speak too soon as it's only been a week but the difference it's made in that short time with redness, oiliness and sensitivity is astonishing. Try and get something with a reasonably high percentage of urea. I started off with a cream that had 10% urea and 5% lactic acid, but felt the lactic acid was slightly irritating so have switched to a gel-cream that's 30%."

    RF has a huge treasure trove of anecdotal reports like this which you can search using the search tool top right corner.
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    Default Montelukast - anyone trialling it?

    I have just been prescribed Montelukast by Prof Chu, do you think it could help with this? Anyone else on it?

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    So they are saying , regardless of how complex the cause is, the end result is simply the activation of mast cells (degranulation) and that is what causes all the symptoms?
    If that is the case taking systemic Gastrocrom 4 times a day for a few months should totally clear up the symptoms (even if it is hitting a walnut with a sledgehammer approach).

  8. #18
    Senior Member Brady Barrows's Avatar
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    Quote Originally Posted by ginaisred View Post
    I have just been prescribed Montelukast by Prof Chu, do you think it could help with this? Anyone else on it?
    Are you taking this orally and what is the dosage?

    "Montelukast is a CysLT1 antagonist; it blocks the action of leukotriene D4 (and secondary ligands LTC4 and LTE4) on the cysteinyl leukotriene receptor CysLT1 in the lungs and bronchial tubes by binding to it. This reduces the bronchoconstriction otherwise caused by the leukotriene and results in less inflammation." Wikipedia

    Maybe someone may comment on whether Montelukast is related to this thread? From my cursory knowledge of this subject it appears to be unrelated. But most of this is over my head, I admit.
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    Senior Member Brady Barrows's Avatar
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    Quote Originally Posted by redtere View Post
    So they are saying , regardless of how complex the cause is, the end result is simply the activation of mast cells (degranulation) and that is what causes all the symptoms?
    If that is the case taking systemic Gastrocrom 4 times a day for a few months should totally clear up the symptoms (even if it is hitting a walnut with a sledgehammer approach).
    It appears you have your head wrapped around this better than me. Gastrocrom is a drug name for Cromoglicic acid. Source

    "Cromoglicic acid (INN) (also referred to as cromolyn (USAN), cromoglycate (former BAN), or cromoglicate) is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. This drug prevents the release of inflammatory chemicals such as histamine from mast cells. Because of their convenience (and perceived safety), leukotriene receptor antagonists have largely replaced it as the non-corticosteroid treatment of choice in the treatment of asthma. Cromoglicic acid requires administration four times daily, and does not provide additive benefit in combination with inhaled corticosteroids." Wikipedia

    ginaisred who is taking Dr. Chu's Montelukast which is a 'leukotriene receptor antagonist' seems to be the "non-corticosteroid treatment of choice in the treatment of asthma." Maybe Dr. Chu is on to something for rosacea?

    But I still don't see the connection of either of these drugs to TRPV4 expression and the Trigeminal sensory malfunction? Can someone explain?
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    Quote Originally Posted by Brady Barrows View Post
    Are you taking this orally and what is the dosage?

    "Montelukast is a CysLT1 antagonist; it blocks the action of leukotriene D4 (and secondary ligands LTC4 and LTE4) on the cysteinyl leukotriene receptor CysLT1 in the lungs and bronchial tubes by binding to it. This reduces the bronchoconstriction otherwise caused by the leukotriene and results in less inflammation." Wikipedia

    Maybe someone may comment on whether Montelukast is related to this thread? From my cursory knowledge of this subject it appears to be unrelated. But most of this is over my head, I admit.
    Thanks Brady, you are way more knowledgable than me on this subject. We shall see, would be great to get everyones opinions on this matter

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