Apfel S C, Arezzo J C, Brownlee M, Federoff H, Kessler J A
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461.
Brain Res. 1994 Jan 14;634(1):7-12. doi: 10.1016/0006-8993(94)90252-6.
Small fiber sensory neuropathy is one of the most common complications of diabetes mellitus. Currently there is no adequate therapy to prevent this often debilitating problem. Nerve growth factor (NGF) is a protein that promotes the survival and integrity of a large percentage of sensory neurons including the small fiber pain transmitting neurons which are often prominently affected in diabetic neuropathy. We report here that exogenously administered NGF is capable of preventing the behavioral and biochemical manifestations of diabetic sensory neuropathy in a streptozocin induced rat model. NGF administration prevented the elevation of tailflick threshold (a measure of the rat's response to a thermal noxious stimulus) which occurred in streptozocin-induced diabetic rats. Further, it prevented the induced reduction in levels of the neuropeptides substance P and calcitonin gene related peptide measured from cervical dorsal root ganglia. Finally, NGF did not ameliorate the prolonged latency of the compound action potentials measured from the caudal nerve of the tail. In view of these results, a clinical trial of NGF in diabetic neuropathy has now commenced.
小纤维感觉神经病变是糖尿病最常见的并发症之一。目前尚无足够的疗法来预防这个常常使人衰弱的问题。神经生长因子(NGF)是一种蛋白质,可促进大部分感觉神经元的存活和完整性,包括在糖尿病神经病变中常受到显著影响的传导疼痛的小纤维神经元。我们在此报告,在链脲佐菌素诱导的大鼠模型中,外源性给予NGF能够预防糖尿病感觉神经病变的行为和生化表现。给予NGF可预防链脲佐菌素诱导的糖尿病大鼠出现的甩尾阈值升高(一种衡量大鼠对热伤害性刺激反应的指标)。此外,它还能预防从颈背根神经节测得的神经肽P物质和降钙素基因相关肽水平的降低。最后,NGF并未改善从尾巴尾神经测得的复合动作电位的延长潜伏期。鉴于这些结果,目前已开始针对糖尿病神经病变进行NGF的临床试验。