Electroacupuncture Alleviates Streptozotocin-Induced Diabetic Neuropathic Pain via the TRPV1-Mediated CaMKII/CREB Pathway in Rats

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Neuroscience Pub Date : 2024-08-20 DOI:10.1007/s12031-024-02256-w

Yinmu Zheng, Siyi Li, Yurong Kang, Qunqi Hu, Yu Zheng, Xiaoxiang Wang, Hengyu Chi, Keying Guo, Minjian Jiang, Zhouyuan Wei, Xiaomei Shao, Chi Xu, Boyu Liu, Junying Du, Xiaofen He, Jianqiao Fang, Zhenzhong Lu, Yongliang Jiang

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Abstract

Diabetic neuropathic pain (DNP) is a diabetic complication that causes severe pain and deeply impacts the quality of the sufferer’s daily life. Currently, contemporary clinical treatments for DNP generally exhibit a deficiency in effectiveness. Electroacupuncture (EA) is recognized as a highly effective and safe treatment for DNP with few side effects. Regrettably, the processes via which EA alleviates DNP are still poorly characterized. Transient receptor potential vanilloid 1 (TRPV1) and phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMKII) are overexpressed on spinal cord dorsal horn (SCDH) in DNP rats, and co-localization is observed between them. Capsazepine, a TRPV1 antagonist, effectively reduced nociceptive hypersensitivity and downregulated the overexpression of phosphorylated CaMKIIα in rats with DNP. Conversely, the CaMKII inhibitor KN-93 did not have any impact on TRPV1. EA alleviated heightened sensitivity to pain caused by nociceptive stimuli and downregulated the level of TRPV1, p-CaMKIIα, and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) in DNP rats. Intrathecal injection of capsaicin, on the other hand, reversed the above effects of EA. These findings indicated that the CaMKII/CREB pathway on SCDH is located downstream of TRPV1 and is affected by TRPV1. EA alleviates DNP through the TRPV1-mediated CaMKII/CREB pathway.

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电针通过 TRPV1 介导的 CaMKII/CREB 通路缓解大鼠链脲佐菌素诱发的糖尿病神经病理性疼痛

糖尿病神经性疼痛（DNP）是一种糖尿病并发症，会引起剧烈疼痛，严重影响患者的日常生活质量。目前，针对 DNP 的当代临床疗法普遍存在疗效不足的问题。电针（EA）是公认的治疗 DNP 的高效、安全且副作用小的疗法。遗憾的是，电针缓解 DNP 的过程仍不甚明了。瞬时受体电位香草素 1（TRPV1）和磷酸化钙/钙调蛋白依赖性蛋白激酶 II（p-CaMKII）在 DNP 大鼠的脊髓背角（SCDH）上过度表达，并且它们之间存在共定位。辣椒素是一种 TRPV1 拮抗剂，它能有效降低 DNP 大鼠的痛觉过敏性，并下调磷酸化 CaMKIIα 的过度表达。相反，CaMKII 抑制剂 KN-93 对 TRPV1 没有任何影响。EA 缓解了 DNP 大鼠对痛觉刺激引起的疼痛敏感性的提高，并下调了 TRPV1、p-CaMKIIα 和磷酸化环磷酸腺苷反应元件结合蛋白（p-CREB）的水平。另一方面，鞘内注射辣椒素可逆转 EA 的上述效应。这些发现表明，SCDH 上的 CaMKII/CREB 通路位于 TRPV1 下游，并受到 TRPV1 的影响。EA通过TRPV1介导的CaMKII/CREB途径缓解DNP。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Neuroscience 医学-神经科学

CiteScore

6.60

自引率

3.20%

发文量

142

审稿时长

1 months

期刊介绍： The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.