Petersen L J, Winge K, Brodin E, Skov P S
Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Denmark.
Clin Exp Allergy. 1997 Aug;27(8):957-65.
Studies in rodents' skin have indicated substance P to be the main inflammatory mediator involved in neurogenic inflammation, acting partly by release of histamine from skin mast cells. The mediators released in neurogenic inflammation in human skin remain to be determined.
To determine the effects of intradermally injected and topically applied capsaicin on the release of histamine and substance P and skin responses in intact human skin in vivo.
Extracellular skin levels of histamine and substance P were measured by microdialysis technique and assayed by enzyme and radio immunoassays. Two kinds of dialysis fibres (210 microm, 2 kDa, and 500 microm, 20 kDa) were inserted intradermally into forearm skin for studies of histamine release to topically administered capsaicin and intradermally injected capsaicin and substance P.
Baseline histamine skin levels were 8.0 +/- 0.7 nM. Intradermally injected capsaicin (0.3-30 microM, 7.5-750 pmol) caused significantly and dose-related flare and pain reactions, but no significant histamine release or weals. Intradermally injected substance P (1 and 3 microM, 25 and 75 pmol) released significant amounts of histamine (peak levels being 90 and 475 nM), evoked weal-and-flare reactions, but did not cause pain. Capsaicin 2% ointment, applied on the skin for 2.5 h, increased skin blood flow by 300-400% as measured by laser Doppler flowmetry, elicited a longstanding burning sensation, but did not release histamine. Substance P-like immunoreactivity (SP-LI) was below the 1.8 pM detection limit following insertion of 20 kDa dialysis fibre and after intradermal injection of capsaicin 3 microM. Intradermal injection of injection of 1 microM of substance P increased SP-LI levels to values greater than 4500 pM, confirming the ability of the dialysis fibre to recover this peptide.
Capsaicin-induced neurogenic activation does not involve the release of histamine from mast cells or detectable amounts of substance P release from sensory nerves in normal human skin in vivo.
对啮齿动物皮肤的研究表明，P物质是参与神经源性炎症的主要炎症介质，其部分作用是通过促使皮肤肥大细胞释放组胺来实现的。人类皮肤神经源性炎症中释放的介质仍有待确定。
确定皮内注射和局部应用辣椒素对体内完整人类皮肤中组胺和P物质释放以及皮肤反应的影响。
采用微透析技术测量皮肤中组胺和P物质的细胞外水平，并通过酶免疫分析和放射免疫分析进行检测。将两种透析纤维（210微米，2千道尔顿，以及500微米，20千道尔顿）皮内插入前臂皮肤，以研究局部应用辣椒素、皮内注射辣椒素和P物质后组胺的释放情况。
组胺的皮肤基线水平为8.0±0.7纳摩尔。皮内注射辣椒素（0.3 - 30微摩尔，7.5 - 750皮摩尔）可引起显著的、与剂量相关的潮红和疼痛反应，但未引起明显的组胺释放或风团。皮内注射P物质（1和3微摩尔，25和75皮摩尔）可释放大量组胺（峰值水平分别为90和475纳摩尔），引发风团和潮红反应，但不引起疼痛。2%辣椒素软膏在皮肤上涂抹2.5小时后，通过激光多普勒血流仪测量，皮肤血流量增加了300 - 400%，引发了持续的灼痛，但未释放组胺。插入20千道尔顿透析纤维后以及皮内注射3微摩尔辣椒素后，P物质样免疫反应性（SP-LI）低于1.8皮摩尔的检测限。皮内注射1微摩尔P物质可使SP-LI水平升高至大于4500皮摩尔的值，证实了透析纤维能够回收该肽。
在正常人类皮肤体内，辣椒素诱导的神经源性激活不涉及肥大细胞释放组胺或感觉神经释放可检测量的P物质。
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