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A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus

Pruriceptive itch originates following activation of peripheral sensory nerve terminals when pruritogens come in contact with the skin. The ability of botulinum neurotoxins (BoNTs) to attenuate transmitter release from afferent terminals provides a rationale for studying its effect on pruritus. This...

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Autores principales: Ramachandran, Roshni, Marino, Marc J., Paul, Snighdha, Wang, Zhenping, Mascarenhas, Nicholas L., Pellett, Sabine, Johnson, Eric A., DiNardo, Anna, Yaksh, Tony L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923300/
https://www.ncbi.nlm.nih.gov/pubmed/29570628
http://dx.doi.org/10.3390/toxins10040134
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author Ramachandran, Roshni
Marino, Marc J.
Paul, Snighdha
Wang, Zhenping
Mascarenhas, Nicholas L.
Pellett, Sabine
Johnson, Eric A.
DiNardo, Anna
Yaksh, Tony L.
author_facet Ramachandran, Roshni
Marino, Marc J.
Paul, Snighdha
Wang, Zhenping
Mascarenhas, Nicholas L.
Pellett, Sabine
Johnson, Eric A.
DiNardo, Anna
Yaksh, Tony L.
author_sort Ramachandran, Roshni
collection PubMed
description Pruriceptive itch originates following activation of peripheral sensory nerve terminals when pruritogens come in contact with the skin. The ability of botulinum neurotoxins (BoNTs) to attenuate transmitter release from afferent terminals provides a rationale for studying its effect on pruritus. This study investigated the effects of BoNT/A1 and BoNT/B1 on mast cell dependent (Compound 48/80:48/80) and independent (Chloroquine:CQ) scratching. C57Bl/6 male mice received intradermal injection of 1.5 U of BoNT/A1, BoNT/B1 or saline 2, 7, 14 and 21 days prior to ipsilateral 48/80 or CQ at the nape of the neck. Ipsilateral hind paw scratching was determined using an automated recording device. The effect of BoNTs on 48/80 mediated mast cell degranulation was analyzed in human and murine mast cells and the presence of SNAREs was determined using qPCR, immunostaining and Western blot. Pre-treatment with BoNT/A1 and BoNT/B1 reduced 48/80 and CQ induced scratching behavior starting on day 2 with reversal by day 21. Both serotypes inhibited 48/80 induced mast cell degranulation. qPCR and immunostaining detected SNAP-25 mRNA and protein, respectively, in mast cells, however, Western blots did not. This study demonstrates the long-lasting anti-pruritic effects of two BoNT serotypes, in a murine pruritus model using two different mechanistically driven pruritogens. These data also indicate that BoNTs may have a direct effect upon mast cell degranulation.
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spelling pubmed-59233002018-05-03 A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus Ramachandran, Roshni Marino, Marc J. Paul, Snighdha Wang, Zhenping Mascarenhas, Nicholas L. Pellett, Sabine Johnson, Eric A. DiNardo, Anna Yaksh, Tony L. Toxins (Basel) Article Pruriceptive itch originates following activation of peripheral sensory nerve terminals when pruritogens come in contact with the skin. The ability of botulinum neurotoxins (BoNTs) to attenuate transmitter release from afferent terminals provides a rationale for studying its effect on pruritus. This study investigated the effects of BoNT/A1 and BoNT/B1 on mast cell dependent (Compound 48/80:48/80) and independent (Chloroquine:CQ) scratching. C57Bl/6 male mice received intradermal injection of 1.5 U of BoNT/A1, BoNT/B1 or saline 2, 7, 14 and 21 days prior to ipsilateral 48/80 or CQ at the nape of the neck. Ipsilateral hind paw scratching was determined using an automated recording device. The effect of BoNTs on 48/80 mediated mast cell degranulation was analyzed in human and murine mast cells and the presence of SNAREs was determined using qPCR, immunostaining and Western blot. Pre-treatment with BoNT/A1 and BoNT/B1 reduced 48/80 and CQ induced scratching behavior starting on day 2 with reversal by day 21. Both serotypes inhibited 48/80 induced mast cell degranulation. qPCR and immunostaining detected SNAP-25 mRNA and protein, respectively, in mast cells, however, Western blots did not. This study demonstrates the long-lasting anti-pruritic effects of two BoNT serotypes, in a murine pruritus model using two different mechanistically driven pruritogens. These data also indicate that BoNTs may have a direct effect upon mast cell degranulation. MDPI 2018-03-23 /pmc/articles/PMC5923300/ /pubmed/29570628 http://dx.doi.org/10.3390/toxins10040134 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ramachandran, Roshni
Marino, Marc J.
Paul, Snighdha
Wang, Zhenping
Mascarenhas, Nicholas L.
Pellett, Sabine
Johnson, Eric A.
DiNardo, Anna
Yaksh, Tony L.
A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus
title A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus
title_full A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus
title_fullStr A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus
title_full_unstemmed A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus
title_short A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus
title_sort study and review of effects of botulinum toxins on mast cell dependent and independent pruritus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923300/
https://www.ncbi.nlm.nih.gov/pubmed/29570628
http://dx.doi.org/10.3390/toxins10040134
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