Department of Life Science, National Taiwan University, Taipei City 10617, Taiwan.
Molecular Imaging Center, National Taiwan University, Taipei City 10051, Taiwan.
Cells. 2020 Nov 4;9(11):2414. doi: 10.3390/cells9112414.
Multiple peripheral nerves are known to degenerate after nerve compression injury but the correlation between the extent of nerve alteration and pain severity remains unclear. Here, we used intravital two-photon fluorescence microscopy to longitudinally observe changes in cutaneous fibers in the hind paw of Nav1.8-Cre-tdTomato mice after chronic constriction injury (CCI). Results showed that the CCI led to variable loss of the skin nerve plexus and intraepidermal nerve fibers. The timing of Nav1.8 nerve fiber loss correlated with the development of mechanical hypersensitivity. We compared a scoring approach that assessed whole-paw nerve degeneration with an index that quantified changes in the nerve plexus and terminals in multiple small regions of interest (ROI) from intravital images of the third and fifth toe tips. We found that the number of surviving nerve fibers was not linearly correlated with mechanical hypersensitivity. On the contrary, at 14 days after CCI, the moderately injured mice showed greater mechanical hypersensitivity than the mildly or severely injured mice. This indicates that both surviving and injured nerves are required for evoked neuropathic pain. In addition, these two methods may have the estimative effect as diagnostic and prognostic biomarkers for the assessment of neuropathic pain.
已知多发性周围神经在神经压迫损伤后会发生退行性变，但神经改变的程度与疼痛严重程度之间的关系尚不清楚。在这里，我们使用活体双光子荧光显微镜纵向观察 Nav1.8-Cre-tdTomato 小鼠慢性缩窄性损伤 (CCI) 后后爪皮肤纤维的变化。结果表明，CCI 导致皮肤神经丛和表皮内神经纤维的可变丢失。Nav1.8 神经纤维丢失的时间与机械性超敏反应的发展相关。我们比较了一种评估整个足神经变性的评分方法和一种指数，该指数量化了活体图像中第三和第五脚趾尖多个小感兴趣区域 (ROI) 中神经丛和末梢的变化。我们发现存活神经纤维的数量与机械性超敏反应没有线性相关性。相反，在 CCI 后 14 天，中度损伤的小鼠比轻度或重度损伤的小鼠表现出更大的机械性超敏反应。这表明，诱发神经性疼痛既需要存活的神经，也需要损伤的神经。此外，这两种方法可能具有诊断和预后生物标志物的评估作用，用于评估神经性疼痛。
