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Toxins 2018, 10(4), 134; https://doi.org/10.3390/toxins10040134

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

1
Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA
2
Department of Medicine, Division of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA
3
Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA
*
Author to whom correspondence should be addressed.
Received: 7 March 2018 / Revised: 21 March 2018 / Accepted: 21 March 2018 / Published: 23 March 2018
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Abstract

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. View Full-Text
Keywords: botulinum toxin; itch; SNARE; VAMP; mast cells; compound 48/80; chloroquine botulinum toxin; itch; SNARE; VAMP; mast cells; compound 48/80; chloroquine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Ramachandran, R.; Marino, M.J.; Paul, S.; Wang, Z.; Mascarenhas, N.L.; Pellett, S.; Johnson, E.A.; DiNardo, A.; Yaksh, T.L. A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus. Toxins 2018, 10, 134.

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