Chen X, Levine J D
Departments of Anatomy, Medicine, and Oral and Maxillofacial Surgery, Division of Neuroscience, NIH Pain Center (UCSF), University of California, San Francisco 94143-0440, USA.
Neuroscience. 2001;102(1):185-92. doi: 10.1016/s0306-4522(00)00454-1.
While clinical characteristics of diabetic painful neuropathy are well described, the underlying electrophysiological basis of the exaggerated painful response to stimuli, as well as the presence of spontaneous pain, are poorly understood. In order to elucidate peripheral contributions to painful diabetic neuropathy, we quantitatively evaluated the function of C-fibers in a rat model of painful diabetic neuropathy, diabetes induced by the pancreatic beta-cell toxin streptozotocin. While there was no significant effect of diabetes on conduction velocity, mechanical threshold or spontaneous activity, the number of action potentials in response to sustained threshold and suprathreshold mechanical stimuli was significantly increased in the diabetic rats. Moreover, there was a clustering of responses of C-fibers in diabetic rats; while two-thirds of C-fibers fired at the same mean frequency as C-fibers in control rats, one-third of C-fibers in diabetic rats were markedly hyper-responsive, demonstrating a threefold increase in firing frequency. The high-firing-frequency C-fibers in rats with diabetes also had faster conduction velocity than the low-firing-frequency C-fibers in rats with diabetes or in C-fibers in control rats. The hyper-responsiveness was characterized by a selective increase of the shortest interspike intervals (<100ms) in the burst component (first 10s) of the response to a sustained suprathreshold stimulus; in the plateau phase (last 50s) of the response to a 60-s suprathreshold stimulus, we found a selective increase of interspike intervals between 100 and 300ms in hyper-responsive C-fibers in rats with diabetes. The hyper-responsiveness did not correlate with mechanical threshold, presence of spontaneous activity or location of the fiber's receptive field. In summary, in an established model of painful diabetic neuropathy in the rat, a subset of C-fibers demonstrated a marked hyper-responsiveness to mechanical stimuli. The subset was also found to have a greater mean conduction velocity than the fibers not demonstrating this hyper-responsivity. The present findings suggest that study of individual neurons in vitro may allow elucidation of the ionic basis of enhanced nociception in diabetic neuropathy.
虽然糖尿病性疼痛性神经病变的临床特征已有充分描述，但对于刺激引起的过度疼痛反应以及自发痛的潜在电生理基础，人们仍知之甚少。为了阐明外周因素对疼痛性糖尿病神经病变的影响，我们在疼痛性糖尿病神经病变大鼠模型中，对C纤维的功能进行了定量评估，该模型通过胰腺β细胞毒素链脲佐菌素诱导糖尿病。虽然糖尿病对传导速度、机械阈值或自发活动没有显著影响，但糖尿病大鼠对持续阈值和阈上机械刺激产生的动作电位数量显著增加。此外，糖尿病大鼠的C纤维反应存在聚类现象；虽然三分之二的C纤维放电频率与对照大鼠的C纤维相同，但糖尿病大鼠中有三分之一的C纤维反应明显增强，放电频率增加了两倍。糖尿病大鼠中高放电频率的C纤维传导速度也比糖尿病大鼠中低放电频率的C纤维或对照大鼠的C纤维更快。这种高反应性的特征是，在对持续阈上刺激的反应爆发成分（最初10秒）中，最短峰间期（<100毫秒）选择性增加；在对60秒阈上刺激的反应平台期（最后50秒），我们发现糖尿病大鼠中高反应性C纤维的峰间期在100至300毫秒之间选择性增加。这种高反应性与机械阈值、自发活动的存在或纤维感受野的位置无关。总之，在已建立的大鼠疼痛性糖尿病神经病变模型中，一部分C纤维对机械刺激表现出明显的高反应性。还发现这部分纤维的平均传导速度比未表现出这种高反应性的纤维更快。目前的研究结果表明，体外对单个神经元进行研究可能有助于阐明糖尿病神经病变中伤害感受增强的离子基础。
