Department of Health Science and Technology, Center for Sensory-Motor Interaction, Aalborg University, Aalborg, Denmark.
BMC Neurosci. 2013 Oct 8;14:116. doi: 10.1186/1471-2202-14-116.
Human nociceptive withdrawal reflexes (NWR) can be evoked by electrical stimulation applied to the sole of the foot. However, elicitation of NWRs is highly site dependent, and NWRs are especially difficult to elicit at the heel. The aim of the present study was to investigate potential peripheral mechanisms for any site dependent differences in reflex thresholds.
The first part of the study investigated the neural innervation in different sites of the sole of the foot using two different staining techniques. 1) Staining for the Nav1.7 antigen (small nociceptive fibers) and 2) the Sihler whole nerve technique (myelinated part of the nerve). No differences in innervation densities were found across the sole of the foot using the two staining techniques: Nav1.7 immunochemistry (small nociceptive fibers (1-way ANOVA, NS)) and the Sihler's method (myelinated nerve fibers (1-way ANOVA, NS)). However, the results indicate that there are no nociceptive intraepidermal nerve fibers (IENFs) innervating the heel.Secondly, mathematical modeling was used to investigate to what degree differences in skin thicknesses affect the activation thresholds of Aδ and Aβ fibers in the sole of the foot. The modeling comprised finite element analysis of the volume conduction combined with a passive model of the activation of branching cutaneous nerve fibers. The model included three different sites in the sole of the foot (forefoot, arch and heel) and three different electrode sizes (diameters: 9.1, 12.9, and 18.3 mm). For each of the 9 combinations of site and electrode size, a total of 3000 Aβ fibers and 300 Aδ fibers was modeled. The computer simulation of the effects of skin thicknesses and innervation densities on thresholds of modeled Aδ and Aβ fibers did not reveal differences in pain and perception thresholds across the foot sole as have been observed experimentally. Instead a lack of IENFs at the heel decreased the electrical activation thresholds compared to models including IENFs.
The nerve staining and modeling results do not explain differences in NWR thresholds across the sole of the foot which may suggest that central mechanisms contribute to variation in NWR excitability across the sole of the foot.
人体伤害性退缩反射(NWR)可以通过施加在脚底的电刺激来引发。然而,NWR 的引出高度依赖于部位,尤其是在脚跟处较难引出。本研究的目的是探究反射阈值的部位依赖性差异的潜在外周机制。
研究的第一部分使用两种不同的染色技术研究了足底不同部位的神经支配。1)Nav1.7 抗原(小伤害性纤维)染色和 2)Sihler 全神经技术(神经的髓鞘部分)。两种染色技术均未发现足底各部位的神经支配密度存在差异:Nav1.7 免疫组织化学(小伤害性纤维(单因素方差分析,NS))和 Sihler 法(有髓神经纤维(单因素方差分析,NS))。然而,结果表明脚跟处没有伤害性表皮内神经纤维(IENFs)支配。其次,数学建模用于探究皮肤厚度的差异在多大程度上影响足底 Aδ 和 Aβ 纤维的激活阈值。该模型包括体积传导的有限元分析以及分支皮肤神经纤维激活的被动模型。该模型包括足底的三个不同部位(前脚、足弓和脚跟)和三个不同的电极尺寸(直径:9.1、12.9 和 18.3mm)。对于每个部位和电极尺寸的 9 种组合,总共模拟了 3000 根 Aβ 纤维和 300 根 Aδ 纤维。对皮肤厚度和神经支配密度对模型化 Aβ 和 Aδ 纤维阈值的影响的计算机模拟并未显示出如实验观察到的那样,足底各部位之间的疼痛和感知阈值存在差异。相反,脚跟处缺乏 IENFs 会降低与包括 IENFs 在内的模型相比的电激活阈值。
神经染色和建模结果无法解释足底 NWR 阈值的差异,这可能表明中枢机制对足底 NWR 兴奋性的变化有贡献。