Department of Health Science and Technology, Faculty of Medicine, Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg University, Aalborg, Denmark.
Department of Dermatology and Allergy, Herlev and Gentofte Hospital, Hellerup, Denmark.
Exp Dermatol. 2022 Sep;31(9):1402-1410. doi: 10.1111/exd.14611. Epub 2022 Jun 2.
Chronic itch is a socioeconomic burden with limited management options. Non-histaminergic itch, involved in problematic pathological itch conditions, is transmitted by a subgroup of polymodal C-fibres. Cowhage is traditionally used for studying experimentally induced non-histaminergic itch in humans but encounters some limitations. The present study, therefore, aims to design a new human, experimental model of non-histaminergic itch based on the application of bovine adrenal medulla (BAM)8-22, an endogenous peptide that activates the MrgprX1 receptor. Twenty-two healthy subjects were recruited. Different concentrations (0.5, 1 and 2 mg/ml) of BAM8-22 solution and vehicle, applied by a single skin prick test (SPT), were tested in the first session. In the second session, the BAM8-22 solution (1 mg/ml) was applied by different number of SPTs (1, 5 and 25) and by heat-inactivated cowhage spicules coated with BAM8-22. Provoked itch and pain intensities were monitored for 9 min, followed by the measurement of superficial blood perfusion (SBP) and mechanical and thermal sensitivities. BAM8-22 induced itch at the concentration of 1, 2 mg/ml (p < 0.05) and with the significantly highest intensity when applied through BAM8-22 spicules (p < 0.001). No concomitant pain sensation or increased SBP was observed. SBP increased only in the 25 SPTs area probably due to microtrauma from the multiple skin penetrations. Mechanical and thermal sensitivities were not affected by any of the applications. BAM8-22 applied through heat-inactivated spicules was the most efficient method to induce itch (without pain or changes in SBP and mechanical and thermal sensitivities) suggesting BAM8-22 as a novel non-histaminergic, human, experimental itch model.
慢性瘙痒是一种具有有限治疗选择的社会经济负担。涉及病理性瘙痒疾病的非组胺性瘙痒由一组多模态 C 纤维传递。刺蒴麻传统上用于研究人类实验性诱导的非组胺性瘙痒，但存在一些局限性。因此，本研究旨在设计一种新的基于牛肾上腺髓质（BAM）8-22 应用的非组胺性瘙痒人类实验模型，BAM8-22 是一种激活 MrgprX1 受体的内源性肽。招募了 22 名健康受试者。在第一次会议中，测试了不同浓度（0.5、1 和 2mg/ml）的 BAM8-22 溶液和载体的单次皮肤点刺试验（SPT）。在第二次会议中，通过不同数量的 SPT（1、5 和 25）和涂有 BAM8-22 的热失活刺蒴麻刺应用 BAM8-22 溶液（1mg/ml）。监测 9 分钟的诱发瘙痒和疼痛强度，然后测量浅表血流灌注（SBP）和机械及热敏感性。在 1、2mg/ml 的浓度下（p<0.05），BAM8-22 引起瘙痒，当用 BAM8-22 刺涂抹时，瘙痒强度显著最高（p<0.001）。没有观察到伴随的疼痛感觉或 SBP 增加。仅在 25 个 SPT 区域观察到 SBP 增加，可能是由于多次皮肤穿透造成的微创伤。机械和热敏感性不受任何应用的影响。应用热失活刺时，BAM8-22 是诱导瘙痒（无疼痛或 SBP 及机械和热敏感性变化）的最有效方法，提示 BAM8-22 可作为一种新的非组胺性、人类实验性瘙痒模型。
