Department of Neurological, Neuropsychological, Morphological and Movement Sciences, Faculty of Medicine, University of Verona, Verona, Italy.
Cell Mol Neurobiol. 2013 Mar;33(2):187-96. doi: 10.1007/s10571-012-9883-6. Epub 2012 Oct 31.
Pharmacological therapies in type 1 diabetes for efficient control of glycemia and changes in pain alterations due to diabetic neuropathy are a continuous challenge. Transient receptor potential vanilloid type 1 (TRPV1) from dorsal root ganglia (DRG) neurons is one of the main pharmacological targets in diabetes, and its ligand capsaicin can be a promising compound for blood-glucose control. Our goal is to elucidate the effect of intraperitoneal (i.p.) capsaicin administration in type 1 diabetic mice against TRPV1 receptors from pancreatic DRG primary afferent neurons. A TCR(+/-)/Ins-HA(+/-) diabetic mice (dTg) was used, and patch-clamp and immunofluorescence microscopy measurements have been performed on thoracic T(9)-T(12) DRG neurons. Capsaicin (800 μg/kg, i.p. three successive days) administration in the late-phase diabetes reduces blood-glucose levels, partly reverses the TRPV1 current density and recovery time constant, without any effect on TRPV1 expression general pattern, in dTg mice. A TRPV1 hypoalgesia profile was observed in late-phase diabetes, which was partly reversed to normoalgesic profile upon capsaicin i.p. administration. According to the soma dimensions of the thoracic DRG neurons, a detailed analysis of the TRPV1 expression upon capsaicin i.p. treatment was done, and the proportion of large A-fiber neurons expressing TRPV1 increased in dTg capsaicin-treated mice. In conclusion, the benefits of low-dose capsaicin intraperitoneal treatment in late-phase type-1 diabetes should be further exploited.
用于有效控制血糖和改变糖尿病神经病变引起的疼痛变化的 1 型糖尿病的药物治疗是一个持续的挑战。背根神经节 (DRG) 神经元中的瞬时受体电位香草酸型 1 (TRPV1) 是糖尿病的主要药物靶点之一,其配体辣椒素可能是控制血糖的有前途的化合物。我们的目标是阐明腹腔内 (i.p.) 辣椒素给药对 1 型糖尿病小鼠胰腺 DRG 初级传入神经元中 TRPV1 受体的影响。使用 TCR(+/-)/Ins-HA(+/-) 糖尿病小鼠 (dTg),并对胸 T(9)-T(12)DRG 神经元进行膜片钳和免疫荧光显微镜测量。在晚期糖尿病中,腹腔内给予辣椒素 (800μg/kg,连续 3 天) 可降低血糖水平,部分逆转 TRPV1 电流密度和恢复时间常数,而对 TRPV1 表达的一般模式没有任何影响在 dTg 小鼠中。在晚期糖尿病中观察到 TRPV1 低敏状态,在腹腔内给予辣椒素后部分逆转至正常敏状态。根据胸 DRG 神经元的体尺寸,对腹腔内给予辣椒素后 TRPV1 的表达进行了详细分析,并且在 dTg 辣椒素处理的小鼠中表达 TRPV1 的大 A 纤维神经元的比例增加。总之,应进一步探索低剂量腹腔内辣椒素治疗晚期 1 型糖尿病的益处。