Neuroscience Technologies, Barcelona, Spain.
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
Eur J Pain. 2018 Sep;22(8):1457-1472. doi: 10.1002/ejp.1235. Epub 2018 May 17.
Peripheral neuropathy is a common complication in type 2 diabetes mellitus (T2DM). The most common presentation is in the form of a distal axonal sensory-motor polyneuropathy that involves large and small nerve fibres in variable proportion.
Zucker Diabetic Fatty (ZDF), Zucker Lean (ZL) and Wistar Han (WH) rats were used to assess the behavioural, morphological and electrophysiological effects that T2DM have on peripheral large and small nerve fibres of 6- to 40-week-old rats.
ZDF rats presented mechanical hypersensitivity that initially worsened in parallel to the progression of diabetes and eventually reverted at later stages of the disease. The reversal from hypersensitivity to hyposensitivity paralleled a reduction in the number of intraepithelial skin nerve terminals and in the nerve fibre lengths. However, no increased levels of degeneration of dorsal root ganglion neurons were observed. Nerve conduction studies showed a reduction in sensory and motor nerve conduction velocity (CV) in hyperglycaemic ZDF rats. Microneurography showed significant alterations in several parameters of activity-dependent slowing (ADS) of mechano-insensitive C-nociceptors in ZDF rats. Surprisingly, some of these changes were also observed in ZL rats. Moreover, we found spontaneous activity in all three strains implying that C-nociceptors become hyperexcitable and spontaneously active not only in ageing hyperglycaemic ZDF rats but also in age-matched and apparently normoglycaemic ZL and WH rats fed with the same diet.
ZDF rats presented a diabetic neuropathy involving large and small nerve fibres; additionally, ZL and WH rats also showed early small abnormalities in C-fibres, clearly detected by microneurography SIGNIFICANCE: This study provides a functional description of large and small nerve fibre function in a diabetic model that recapitulates many of the findings observed in patients suffering from type 2 diabetes mellitus.
周围神经病变是 2 型糖尿病（T2DM）的常见并发症。最常见的表现是远端轴索性感觉运动多发性神经病，涉及大、小神经纤维，比例不同。
使用 Zucker 糖尿病肥胖（ZDF）、Zucker 瘦型（ZL）和 Wistar Han（WH）大鼠评估 T2DM 对 6-40 周龄大鼠周围大、小神经纤维的行为、形态和电生理影响。
ZDF 大鼠表现出机械性超敏，最初与糖尿病的进展平行恶化，最终在疾病的后期阶段恢复。从超敏反应到低敏反应的逆转与上皮内皮肤神经末梢数量和神经纤维长度的减少相平行。然而，没有观察到背根神经节神经元退行性变的增加。神经传导研究显示，高血糖 ZDF 大鼠的感觉和运动神经传导速度（CV）降低。微神经生理学显示，ZDF 大鼠机械性感觉迟钝 C 伤害感受器的活动依赖性减慢（ADS）的几个参数发生了显著变化。令人惊讶的是，ZL 大鼠也观察到了其中一些变化。此外，我们发现所有三种品系的自发性活动，这意味着 C 伤害感受器不仅在衰老的高血糖 ZDF 大鼠中变得过度兴奋和自发性活跃，而且在年龄匹配且显然正常血糖的 ZL 和 WH 大鼠中也变得过度兴奋和自发性活跃，这些大鼠喂食相同的饮食。
ZDF 大鼠表现出大、小神经纤维的糖尿病性神经病；此外，ZL 和 WH 大鼠也表现出 C 纤维的早期小异常，微神经生理学清楚地检测到这一点。
本研究提供了一种在糖尿病模型中大、小神经纤维功能的功能描述，该模型重现了许多在 2 型糖尿病患者中观察到的发现。
