Peptide-mediated transdermal delivery of botulinum neurotoxin type A reduces neurogenic inflammation in the skin
Peptide-mediated transdermal delivery of botulinum neurotoxin type A reduces neurogenic inflammation in the skin
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DOI：
10.1016/j.pain.2010.02.024
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发表时间：
2010-05-01
期刊：
影响因子：
7.4
通讯作者：
Charlton, Milton P.
中科院分区：
文献类型：
--
作者：
Carmichael, Nicole M. E.;Dostrovsky, Jonathan O.;Charlton, Milton P.
从外周感觉传入末梢释放炎性疼痛介质有助于形成一个正反馈循环，从而导致慢性炎症和疼痛。A型肉毒神经毒素(BoNT-A)阻止神经递质的胞吐，因此可能阻止外周疼痛调节剂的释放。皮下注射BoNT-A(2.5、5和10U)可减少电刺激大鼠后爪皮肤隐神经或辣椒素所引起的血浆外渗(PE)(ANOVA，Post hoc Tukey，p<；0.05，n=6)。皮下BONT-A也减少了隐神经刺激引起的血流量变化(ANOVA，Post hoc Tukey，p<；0.05，n=6)。皮下注射Bont-A对局部注射P物质(SP)或局部注射CGRP引起的血管扩张均无影响。虽然BoNT-A是一种治疗各种疼痛的有效方法，但这种毒素的体积很大，因此必须在许多部位注射。我们发现，一个短的合成肽(TD-1)可以促进BoNT-A通过完整皮肤的有效透皮吸收。将TD-1和BONT-A联合应用于后足皮肤，可显著降低电刺激诱发的PE。研究结果表明，BoNT-A可以与一种新型的透皮递送肽一起皮下或局部使用，以减少因激活皮肤中的伤害性感受器而产生的炎症。多肽介导的BoNT-A递送是一种简单且非侵入性的毒素给药方式，可能在临床实践中被证明是有用的。(C)2010年国际疼痛研究协会。爱思唯尔出版公司版权所有。
Release of inflammatory pain mediators from peripheral sensory afferent endings contributes to the development of a positive feedback cycle resulting in chronic inflammation and pain. Botulinum neurotoxin type A (BoNT-A) blocks exocytosis of neurotransmitters and may therefore block the release of pain modulators in the periphery. Subcutaneous administration of BoNT-A (2.5, 5 and 10 U) reduced plasma extravasation (PE) caused by electrical stimulation of the saphenous nerve or capsaicin in the rat hind-paw skin (ANOVA, Post hoc Tukey, p < 0.05, n = 6). Subcutaneous BoNT-A also reduced blood flow changes evoked by saphenous nerve stimulation (ANOVA, Post hoc Tukey, p < 0.05, n = 6). Subcutaneous BoNT-A had no effect on PE induced by local injection of substance P (SP) or vasodilation induced by local CGRP injection. Although BoNT-A is an effective treatment for a wide range of painful conditions, the toxin's large size necessitates that it be injected at numerous sites. We found that a short synthetic peptide (TD-1) can facilitate effective transdermal delivery of BoNT-A through intact skin. Coadministration of TD-1 and BoNT-A to the hindpaw skin resulted in a significant reduction in PE evoked by electrical stimulation. The findings show that BoNT-A can be administered subcutaneously or topically with a novel transdermal delivery peptide to reduce inflammation produced by activating nociceptors in the skin. Peptide-mediated delivery of BoNT-A is an easy and non-invasive way of administering the toxin that may prove to be useful in clinical practice. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.