Newton Victoria L, Guck Jonathan D, Cotter Mary A, Cameron Norman E, Gardiner Natalie J
Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
School of Medical Sciences, University of Aberdeen, Aberdeen, UK.
J Diabetes Res. 2017;2017:4729284. doi: 10.1155/2017/4729284. Epub 2017 Feb 15.
Spinal glial cell activation and cytokine secretion have been implicated in the etiology of neuropathic pain in a number of experimental models, including diabetic neuropathy. In this study, streptozotocin- (STZ-) induced diabetic rats were either untreated or treated with gabapentin (50 mg/kg/day by gavage for 2 weeks, from 6 weeks after STZ). At 8 weeks after STZ, hypersensitivity was confirmed in the untreated diabetic rats as a reduced response threshold to touch, whilst mechanical thresholds in gabapentin-treated diabetic rats were no different from controls. Diabetes-associated thermal hypersensitivity was also ameliorated by gabapentin. We performed a cytokine profiling array in lumbar spinal cord samples from control and diabetic rats. This revealed an increase in L-selectin, an adhesion molecule important for neutrophil transmigration, in the spinal cord of diabetic rats but not diabetic rats treated with gabapentin. Furthermore, we found an increase in the number of neutrophils present in the parenchyma of the spinal cord, which was again ameliorated in gabapentin-treated diabetic rats. Therefore, we suggest that dysregulated spinal L-selectin and neutrophil infiltration into the spinal cord could contribute to the pathogenesis of painful diabetic neuropathy.
在包括糖尿病性神经病变在内的许多实验模型中，脊髓胶质细胞活化和细胞因子分泌与神经性疼痛的病因学有关。在本研究中，将链脲佐菌素（STZ）诱导的糖尿病大鼠分为未治疗组或加巴喷丁治疗组（自STZ注射后6周起，通过灌胃给予50 mg/kg/天，持续2周）。在STZ注射后8周，未治疗的糖尿病大鼠表现出超敏反应，即对触摸的反应阈值降低，而加巴喷丁治疗的糖尿病大鼠的机械阈值与对照组无差异。加巴喷丁还改善了与糖尿病相关的热超敏反应。我们对对照组和糖尿病大鼠的腰段脊髓样本进行了细胞因子谱阵列分析。结果显示，糖尿病大鼠脊髓中对中性粒细胞迁移很重要的黏附分子L-选择素增加，而加巴喷丁治疗的糖尿病大鼠则未出现这种情况。此外，我们发现脊髓实质中的中性粒细胞数量增加，加巴喷丁治疗的糖尿病大鼠再次出现改善。因此，我们认为脊髓L-选择素失调和中性粒细胞浸润脊髓可能促成疼痛性糖尿病神经病变的发病机制。
