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

  • J Mol Neurosci. 2024 Aug 20;74(3):79. doi: 10.1007/s12031-024-02256-w.
Yinmu Zheng  #  1  2 ,  Siyi Li  #  1  2 ,  Yurong Kang  1  2 ,  Qunqi Hu  1  2 ,  Yu Zheng  1  2 ,  Xiaoxiang Wang  2 ,  Hengyu Chi  2 ,  Keying Guo  2 ,  Minjian Jiang  1  2 ,  Zhouyuan Wei  1  2 ,  Xiaomei Shao  1  2 ,  Chi Xu  1  2 ,  Boyu Liu  1  2 ,  Junying Du  1  2 ,  Xiaofen He  1  2 ,  Jianqiao Fang  1  2 ,  Zhenzhong Lu  3 ,  Yongliang Jiang  4  5
Affiliations
  • 1. Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
  • 2. The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
  • 3. Jinhua Wenrong Hospital, Jinhua, China. [email protected].
  • 4. Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China. [email protected].
  • 5. The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China. [email protected].
  • # Contributed equally.
PMID: 39162890 DOI: 10.1007/s12031-024-02256-w
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.

Keywords
CaMKII/CREB pathway; Capsaicin; Capsazepine; Diabetic neuropathic pain; KN-93; TRPV1.
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