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

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.

Botulinum Toxin Type B for Hidradenitis Suppurativa: A Randomised, Double-Blind, Placebo-Controlled Pilot Study

“…BTX inhibits neurogenic inflammation by attenuation of neurotransmitter release (glutamate, substance P and calcitonin gene-related peptide) and reduction of inflammatory cell infiltration [ 31 – 34 ]. Furthermore, the nociceptive innervation of mast cells is also inhibited by BTX-B [ 35 ]. Mast cells are present, to a greater degree, in HS lesions than in perilesional skin, and, in a recent paper, disease severity has been shown to correlate with the number of mast cells and with itch [ 36 ].…”

Botulinum toxin type A in chronic non‐dyshidrotic palmar eczema: A side‐by‐side comparative study

“…Additionally, it inhibited mast cell degranulation and the release of pruritogenic mediators in both human and murine mast cells, with inhibition of mast cell‐dependent and ‐independent scratching behavior in pretreated mice 25 . It downregulated the expression of the itch receptors’ transient receptor potential cation channel, subfamily A, member 1 (TRPA1) and subfamily V, member 1 (TRPV1), in the dorsal root ganglia in a mouse model of chronic dry itch leading to long‐term amelioration of itching 26 .…”

Botulinum Neurotoxin Type A in the Treatment of Oily Skin and Acne: Evidence and a Proposed Mechanism

“…Inflammatory acne lesions show an increased number and activity of mast cells in their SGs [65] [74]. BoNTA inhibits mast cell activity by affecting soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) proteins, including synaptosomal-associated protein-25 (SNAP-25) and vesicle-associated membrane protein (VAMP) [75]. BoNTA also inhibits signaling of the transient receptor potential vanilloid subtype 1 (TRPV1) [76], which is a regulator of human sebocyte activities and the disease process of acne [77][78].…”