Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA.
Department of Medicine, Division of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA.
Toxins (Basel). 2018 Mar 23;10(4):134. doi: 10.3390/toxins10040134.
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.
瘙痒起源于感觉神经末梢被激活后，当瘙痒原与皮肤接触时。肉毒毒素（BoNTs）通过减弱传入末梢递质释放的能力为研究其对瘙痒的影响提供了理论依据。本研究调查了 BoNT/A1 和 BoNT/B1 对肥大细胞依赖性（化合物 48/80：48/80）和独立性（氯喹：CQ）搔抓的影响。C57Bl/6 雄性小鼠在颈背部皮内注射 1.5 U 的 BoNT/A1、BoNT/B1 或生理盐水，2、7、14 和 21 天后同侧注射 48/80 或 CQ。使用自动记录装置测定同侧后爪搔抓。分析了 BoNTs 对人类和鼠肥大细胞中 48/80 介导的肥大细胞脱颗粒的作用，并通过 qPCR、免疫染色和 Western blot 检测 SNAREs 的存在。BoNT/A1 和 BoNT/B1 的预处理可减少 48/80 和 CQ 诱导的搔抓行为，从第 2 天开始，第 21 天逆转。两种血清型均抑制 48/80 诱导的肥大细胞脱颗粒。qPCR 和免疫染色分别检测到肥大细胞中的 SNAP-25 mRNA 和蛋白，但 Western blot 没有。本研究在两种不同机械驱动瘙痒原的小鼠瘙痒模型中，证明了两种 BoNT 血清型的持久抗瘙痒作用。这些数据还表明，BoNTs 可能对肥大细胞脱颗粒有直接影响。
