首页> 外文期刊>Neuroscience: An International Journal under the Editorial Direction of IBRO >THE EFFECTS OF INTRAGANGLIONIC INJECTION OF CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE II INHIBITORS ON PAIN-RELATED BEHAVIOR IN DIABETIC NEUROPATHY
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THE EFFECTS OF INTRAGANGLIONIC INJECTION OF CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE II INHIBITORS ON PAIN-RELATED BEHAVIOR IN DIABETIC NEUROPATHY

机译:肝内注射钙/钙调蛋白依赖性蛋白激酶II抑制剂对糖尿病神经痛患者疼痛相关行为的影响

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Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the transmission of nocicep-tive input in diabetic neuropathy. The aim of this study was to test whether intraganglionic (i.g.) injection of CaMKII inhibitors may alleviate pain-related behavior in diabetic rats. Diabetes was induced in Sprague-Dawley rats using 55 mg/kg streptozotocin intraperitoneally. Two weeks after diabetes induction, CaMKII inhibitors myristoil-AlP and KN93 were injected directly into the right L5 dorsal root ganglion (DRG). Behavioral testing with mechanical and thermal stimuli was performed before induction of diabetes, the day preceding the injection, as well as 2 and 24 h after the i.g. injection. The expression of total CaMKII and its alpha isoform in DRG neurons was analyzed using immunohistochemistry. CaMKII inhibitors attenuated pain-related behavior in a modality-specific fashion. Attenuation of nociceptive behavior was accompanied with a corresponding decrease of CaMKII alpha expression in DRG neurons on the side of injection. A significant decrease of CaMKII alpha expression was seen in small- and medium-sized neurons. In conclusion, our study provides evidence that CaMKII inhibitors are potential pharmacological agents that should be further explored for treatment of diabetic neuropathy symptoms.
机译:钙/钙调蛋白依赖性蛋白激酶II(CaMKII)已牵涉到糖尿病性神经病中夜觉性输入的传递。这项研究的目的是测试神经节内(例如)注射CaMKII抑制剂是否可以减轻糖尿病大鼠的疼痛相关行为。使用55 mg / kg链脲佐菌素腹膜内在Sprague-Dawley大鼠中诱发糖尿病。诱导糖尿病两周后,将CaMKII抑制剂myristoil-AlP和KN93直接注射到右L5背根神经节(DRG)中。用机械和热刺激进行行为测试是在诱导糖尿病前,注射前一天以及注射后2小时和24小时进行的。注射。使用免疫组织化学分析了DRG神经元中总CaMKII及其α同工型的表达。 CaMKII抑制剂以一种特定于形式的方式减弱了与疼痛有关的行为。注射侧DRG神经元中伤害性行为的减弱伴随着CaMKIIα表达的相应降低。在中小型神经元中发现CaMKIIα表达显着下降。总之,我们的研究提供了证据,表明CaMKII抑制剂是潜在的药理学药物,应进一步探索以治疗糖尿病性神经病症状。

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