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健康男性远端周围神经末梢 TRP 通道功能的血管读出。

Vascular read-out for TRP channel functionality on distal peripheral nerve endings in healthy men.

机构信息

Center for Clinical Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.

Center for Clinical Pharmacology, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.

出版信息

Microvasc Res. 2024 Mar;152:104654. doi: 10.1016/j.mvr.2024.104654. Epub 2024 Jan 10.

Abstract

BACKGROUND

Quantification of the vasodilation after topical application of capsaicin or cinnamaldehyde is often implemented to indirectly assess Transient Receptor Potential (TRP) Vanilloid 1 (TRPV1) or Ankyrin 1 (TRPA1) functionality respectively. This method has been well-established on the human forearm. However, to enable TRP functionality assessments in distal peripheral neuropathy, the vascular response upon TRP activation on dorsal finger skin was characterized.

METHODS

Two doses of cinnamaldehyde (3 % and 10 % v/v) and capsaicin (300 μg and 1000 μg) were topically applied (20 μL) on the skin of the mid three proximal phalanges in 17 healthy men. The dose-response, and inter-hand and inter-period reproducibility of the dermal blood flow (DBF) increase was assessed using Laser Speckle Contrast Imaging (LSCI) during 60 min post-application. Linear mixed models explored dose-driven differences, whereas the intra-class correlation coefficient (ICC) estimated the reproducibility of the vascular response.

RESULTS

Both doses of cinnamaldehyde and capsaicin induced a robust, dose-dependent increase in DBF. The vascular response to cinnamaldehyde 10 % on finger skin, expressed as area under the curve, correlated well over time (ICC = 0.66) and excellently between hands (ICC = 0.87). Similarly, the response to capsaicin 1000 μg correlated moderately over time (ICC = 0.50) and well between hands (ICC = 0.73).

CONCLUSION

The vascular response upon topical cinnamaldehyde and capsaicin application on finger skin is an alternative approach for measurements on forearm skin. Thereby, it is a promising vascular read-out to investigate the pathophysiology, and TRP involvement in particular, of specific peripheral neuropathic pain syndromes.

摘要

背景

通过测量辣椒素或肉桂醛涂敷后的血管扩张程度,可以间接评估瞬时受体电位香草醛 1 型(TRPV1)或锚蛋白 1 型(TRPA1)的功能。这种方法已在人体前臂得到了很好的验证。然而,为了在远端周围神经病变中评估 TRP 的功能,我们对背侧手指皮肤在 TRP 激活后的血管反应进行了特征描述。

方法

将两种剂量的肉桂醛(3%和 10%v/v)和辣椒素(300μg 和 1000μg)分别涂敷于 17 名健康男性中指近 3 个近端指节的皮肤,采用激光散斑对比成像(LSCI)技术,在涂药后 60 分钟内评估皮肤血流量(DBF)的剂量反应和双手间及两期之间的可重复性。线性混合模型用于探索剂量依赖性差异,而组内相关系数(ICC)用于评估血管反应的可重复性。

结果

肉桂醛和辣椒素的两种剂量均能引起强烈的、剂量依赖性的 DBF 增加。手指皮肤涂敷 10%肉桂醛后的血管反应(以曲线下面积表示)在时间上相关性较好(ICC=0.66),在双手间相关性极好(ICC=0.87)。同样,涂敷 1000μg 辣椒素后的反应在时间上中度相关(ICC=0.50),在双手间相关性较好(ICC=0.73)。

结论

手指皮肤涂敷肉桂醛和辣椒素后引起的血管反应是前臂皮肤测量的替代方法。因此,它是一种很有前途的血管反应指标,可以用于研究特定周围神经病理性疼痛综合征的病理生理学,特别是 TRP 的参与情况。

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