Decreased Endomorphin-2 and μ-Opioid Receptor in the Spinal Cord Are Associated with Painful Diabetic Neuropathy.

Decreased Endomorphin-2 and μ-Opioid Receptor in the Spinal Cord Are Associated with Painful Diabetic Neuropathy.
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脊髓内吗啡-2 和 mu-阿片受体的减少与疼痛性糖尿病神经病变有关。

DOI:
10.3389/fnmol.2016.00080
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发表时间:
2016
影响因子:
4.8
通讯作者:
Li YQ
Li YQ
中科院分区:
医学2区
文献类型:
--
作者:
Kou ZZ;Wan FP;Bai Y;Li CY;Hu JC;Zhang GT;Zhang T;Chen T;Wang YY;Li H;Li YQ

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疼痛性糖尿病神经病变(PDN)是糖尿病(DM)早期最常见的并发症之一。 Endomorphin-2 (EM2) 选择性激活 μ-阿片受体 (MOR),随后在脊髓背角诱导镇痛作用。然而,EM2-MOR 在 PDN 中的作用尚未在脊髓背角中阐明。因此,我们旨在探讨EM2-MOR在PDN发病机制中的作用。主要发现如下:(1)链脲佐菌素(STZ)诱导的糖尿病大鼠表现出高血糖、体重减轻和机械性异常性疼痛; (2)糖尿病大鼠脊髓背角中EM2和MOR的表达水平降低; (3)糖尿病大鼠脑、腰脊髓和脑脊液(CSF)中EM2蛋白浓度降低,但血浆中无变化; (4)糖尿病大鼠自发兴奋性突触后电流(sEPSC)的频率显着高于对照大鼠,但幅度不显着; (5)PDN早期鞘内注射EM2 14天可部分缓解糖尿病大鼠机械性异常性疼痛并降低MOR表达。我们的结果表明EM2-MOR信号可能参与PDN的早期阶段。
Painful diabetic neuropathy (PDN) is one of the most common complications in the early stage of diabetes mellitus (DM). Endomorphin-2 (EM2) selectively activates the μ-opioid receptor (MOR) and subsequently induces antinociceptive effects in the spinal dorsal horn. However, the effects of EM2-MOR in PDN have not yet been clarified in the spinal dorsal horn. Therefore, we aimed to explore the role of EM2-MOR in the pathogenesis of PDN. The main findings were the following: (1) streptozotocin (STZ)-induced diabetic rats exhibited hyperglycemia, body weight loss and mechanical allodynia; (2) in the spinal dorsal horn, the expression levels of EM2 and MOR decreased in diabetic rats; (3) EM2 protein concentrations decreased in the brain, lumbar spinal cord and cerebrospinal fluid (CSF) in diabetic rats but were unchanged in the plasma; (4) the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) was significantly higher in diabetic rats than in control rats; and (5) intrathecal injection of EM2 for 14 days in the early stage of PDN partially alleviated mechanical allodynia and reduced MOR expression in diabetic rats. Our results demonstrate that the EM2-MOR signal may be involved in the early stage of PDN.
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