Department of Life Science, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan.
J Comp Neurol. 2021 Aug;529(12):3247-3264. doi: 10.1002/cne.25162. Epub 2021 May 4.
Neuropathic pain is pain caused by damage to the somatosensory nervous system. Both degenerating injured nerves and neighboring sprouting nerves can contribute to neuropathic pain. However, the mesoscale changes in cutaneous nerve fibers over time after the loss of the parent nerve has not been investigated in detail. In this study, we followed the changes in nerve fibers longitudinally in the toe tips of mice that had undergone spared nerve injury (SNI). Nav1.8-tdTomato, Thy1-GFP and MrgD-GFP mice were used to observe the small and large cutaneous nerve fibers. We found that peripheral nerve plexuses degenerated within 3 days of nerve injury, and free nerve endings in the epidermis degenerated within 2 days. The timing of degeneration paralleled the initiation of mechanical hypersensitivity. We also found that some of the Nav1.8-positive nerve plexuses and free nerve endings in the fifth toe survived, and sprouting occurred mostly from 7 to 28 days. The timing of the sprouting of nerve fibers in the fifth toe paralleled the maintenance phase of mechanical hypersensitivity. Our results support the hypotheses that both injured and intact nerve fibers participate in neuropathic pain, and that, specifically, nerve degeneration is related to the initiation of evoked pain and nerve sprouting is related to the maintenance of evoked pain.
神经病理性疼痛是由躯体感觉神经系统损伤引起的疼痛。退化损伤的神经和邻近的新生神经都可能导致神经病理性疼痛。然而，在失去母体神经后，皮肤神经纤维的中尺度变化尚未得到详细研究。在这项研究中，我们对接受 spared nerve injury (SNI) 的小鼠的脚趾尖的神经纤维进行了纵向观察。使用 Nav1.8-tdTomato、Thy1-GFP 和 MrgD-GFP 小鼠来观察小和大的皮肤神经纤维。我们发现，神经损伤后 3 天内周围神经丛发生退化，表皮中的游离神经末梢在 2 天内退化。退化的时间与机械性超敏反应的开始相吻合。我们还发现，第五趾的一些 Nav1.8 阳性神经丛和游离神经末梢存活下来，并且从第 7 天到第 28 天主要发生了神经纤维的发芽。第五趾神经纤维发芽的时间与机械性超敏反应的维持阶段相吻合。我们的结果支持以下假说：受损和完整的神经纤维都参与神经病理性疼痛，具体来说，神经退化与诱发疼痛的开始有关，而神经发芽与诱发疼痛的维持有关。
