Unité READ, Faculty of Medicine, Université catholique de Louvain, Brussels, Belgium.
Clin Neurophysiol. 2010 Aug;121(8):1256-66. doi: 10.1016/j.clinph.2010.02.159. Epub 2010 Mar 26.
To assess the temporal relationship between skin nerve denervation and regeneration (dermal and intra-epidermal fibres, IENF) and functional changes (CO(2) laser-evoked potentials, LEPs, and quantitative sensory tests, QST) after topical cutaneous application of capsaicin.
Capsaicin (0.075%) was applied to the lateral calf for three consecutive days. QST, LEPs and skin biopsies were performed at baseline and time intervals up to 54days post-capsaicin treatment. Biopsies were immunostained with antibodies for PGP9.5, TRPV1, and GAP-43 (marker of regenerating nerve fibres), and analyzed for IENFs and dermal innervation (for GAP-43).
At 1day post-capsaicin, cutaneous thermal sensitivity was reduced, as were LEPs. PGP9.5, TRPV1, and GAP-43 immunoreactive-nerve fibres were almost completely absent. By Day 12, LEPs had fully recovered, but PGP9.5 and TRPV1 IENF continued to be significantly decreased 54days post-capsaicin. In contrast, dermal GAP-43 immunoreactivity closely matched recovery of LEPs.
A good correlation was observed between LEPs and GAP-43 staining, in contrast to PGP9.5 and TRPV1. Laser stimulation is a non-invasive and sensitive method for assessing the initial IENF loss, and regenerating nerve fibres.
Assessing skin biopsies by PGP9.5 immunostaining alone may miss significant diagnostic and prognostic information regarding regenerating nerve fibres, if other approaches are neglected, e.g. LEPs or GAP-43 immunostaining.
评估皮肤神经去神经支配和再生(真皮和表皮内纤维,IENF)与功能变化(CO2 激光诱发电位,LEP 和定量感觉测试,QST)之间的时间关系,外用辣椒素后。
将辣椒素(0.075%)连续 3 天涂于小腿外侧。在基线和辣椒素治疗后长达 54 天的时间间隔内进行 QST、LEP 和皮肤活检。用针对 PGP9.5、TRPV1 和 GAP-43(再生神经纤维的标志物)的抗体对活检进行免疫染色,并分析 IENF 和真皮神经支配(用于 GAP-43)。
在辣椒素治疗后 1 天,皮肤热敏感性降低,LEP 降低。PGP9.5、TRPV1 和 GAP-43 免疫反应性神经纤维几乎完全消失。到第 12 天,LEP 已完全恢复,但 PGP9.5 和 TRPV1 IENF 在辣椒素治疗后 54 天仍显著降低。相比之下,真皮 GAP-43 免疫反应性与 LEP 的恢复密切相关。
LEP 与 GAP-43 染色之间观察到良好的相关性,与 PGP9.5 和 TRPV1 形成对比。激光刺激是评估初始 IENF 丢失和再生神经纤维的非侵入性和敏感方法。
如果忽略其他方法,例如 LEP 或 GAP-43 免疫染色,仅通过 PGP9.5 免疫染色评估皮肤活检可能会错过有关再生神经纤维的重要诊断和预后信息。