Department of Anesthesia, Stanford University, Palo Alto, CA, USA.
Lasmed LLC, Mountain View, CA, USA.
Curr Diabetes Rev. 2022;18(5):e081221198649. doi: 10.2174/1573399818666211208101555.
The cutaneous mechanisms that trigger spontaneous neuropathic pain in diabetic peripheral neuropathy (PDPN) are far from clear. Two types of nociceptors are found within the epidermal and dermal skin layers. Small-diameter lightly myelinated Aδ and unmyelinated C cutaneous mechano and heat-sensitive (AMH and CMH) and C mechanoinsensitive (CMi) nociceptors transmit pain from the periphery to central nervous system. AMH and CMH fibers are mainly located in the epidermis, and CMi fibers are distributed in the dermis. In DPN, dying back intra-epidermal AMH and CMH fibers leads to reduced pain sensitivity, and the patients exhibit significantly increased pain thresholds to acute pain when tested using traditional methods. The role of CMi fibers in painful neuropathies has not been fully explored. Microneurography has been the only tool to access CMi fibers and differentiate AMH, CMH, and CMi fiber types. Due to the complexity, its use is impractical in clinical settings. In contrast, a newly developed diode laser fiber selective stimulation (DLss) technique allows to safely and selectively stimulate Aδ and C fibers in the superficial and deep skin layers. DLss data demonstrate that patients with painful DPN have increased Aδ fiber pain thresholds, while C-fiber thresholds are intact because, in these patients, CMi fibers are abnormally spontaneously active. It is also possible to determine the involvement of CMi fibers by measuring the area of DLss-induced neurogenic axon reflex flare. The differences in AMH, CMH, and CMi fibers identify patients with painful and painless neuropathy. In this review, we will discuss the role of CMi fibers in PDPN.
自发性神经病理性疼痛触发机制在糖尿病周围神经病变（DPNP）中仍不清楚。表皮和真皮皮肤层内存在两种类型的伤害感受器。小直径轻度髓鞘 Aδ 和无髓鞘 C 机械和热敏（AMH 和 CMH）和 C 机械不敏感（CMi）伤害感受器将疼痛从外周传递到中枢神经系统。AMH 和 CMH 纤维主要位于表皮，CMi 纤维分布于真皮。在 DPN 中，表皮内 AMH 和 CMH 纤维的退行性变导致疼痛敏感性降低，并且当使用传统方法进行测试时，患者对急性疼痛的疼痛阈值显著增加。CMi 纤维在痛性神经病变中的作用尚未得到充分探索。微神经生理学一直是唯一可以访问 CMi 纤维并区分 AMH、CMH 和 CMi 纤维类型的工具。由于其复杂性，在临床环境中使用不切实际。相比之下，新开发的二极管激光纤维选择性刺激（DLss）技术允许安全且选择性地刺激浅表和深层皮肤层中的 Aδ 和 C 纤维。DLss 数据表明，患有痛性 DPN 的患者的 Aδ 纤维疼痛阈值增加，而 C 纤维阈值正常，因为在这些患者中，CMi 纤维异常自发性活跃。通过测量 DLss 诱导的神经源性轴突反射闪光的面积，也可以确定 CMi 纤维的参与。AMH、CMH 和 CMi 纤维的差异可识别有痛和无痛性神经病变的患者。在这篇综述中，我们将讨论 CMi 纤维在 DPNP 中的作用。
