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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1439448
This article is part of the Research Topic 'Pain and pain-related neuropsychiatric disorders: from mechanistic insights to innovative therapeutic strategies.' View all 7 articles

Hemoglobin α Derived Peptides VD-hemopressin (α) and RVD-hemopressin (α) are Involved in Electroacupuncture Inhibition of Chronic Pain

Provisionally accepted
Xiaocui Yuan Xiaocui Yuan 1Yixiao Guo Yixiao Guo 1Huiyuan Yi Huiyuan Yi 1Xuemei Hou Xuemei Hou 1Yulong Zhao Yulong Zhao 1Yuying Wang Yuying Wang 1Hong Jia Hong Jia 1Sani S. Baba Sani S. Baba 2Man Li Man Li 3*Fu-Quan Huo Fu-Quan Huo 1*
  • 1 Department of Physiology and Pathophysiology, School of Basic Medicine, Xi'an Jiaotong University, Xi'an, China
  • 2 College of Health Sciences, Bayero University Kano, Kano, Nigeria
  • 3 School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China

The final, formatted version of the article will be published soon.

    Knee osteoarthritis (KOA) is a chronic degenerative bone metabolic disease that primarily affects elderly adults, leading to chronic pain and disability which affect patients’ daily activities. Electroacupuncture (EA) is a commonly used method for the treatment of chronic pain in clinical practice. Previous studies indicate that endocannabinoid system is involved in EA analgesia, but whether endocannabinopeptide VD-hemopressin (α) and RVD-hemopressin (α), derived from hemoglobin chains are involved in EA analgesia is unclear. Therefore, we used RNA-seq to obtain differentially expressed genes Hba-a1 and Hba-a2 involved in EA analgesia in the periaqueductal grey (PAG), which were translated into hemoglobin α chain. EA significantly increased the expression of hemoglobin α chain and the level of hemopressin (α) and RVD-hemopressin (α). Microinjection of VD-hemopressin (α) and RVD-hemopressin (α) into vlPAG mimicked the analgesic effect of EA, while CB1 receptor antagonist AM251 reversed this effect. EA significantly increased the expression of 26S proteasome in KOA mice. Microinjection of 26S proteasome inhibitor MG132 before EA, prevented both anti-allodynic effect and up-regulation the concentration of RVD-hemopressin (α) by EA treatment, and up-regulated the expression of hemoglobin α chain. Our data suggest that EA up-regulated the concentration of VD-hemopressin (α) and RVD-hemopressin (α) through enhancement of the hemoglobin α chain degradation by 26S proteasome in PAG, then activated the CB1 receptor, thereby exerting inhibition of chronic pain in a mouse model of KOA. These results provide new insights into the EA analgesic mechanisms and evidently reveal possible targets for EA treatment of chronic pain.

    Keywords: EA, Electroacupuncture, KOA, Knee osteoarthritis, PAG, periaqueductal grey, AEA, arachidonic ethanolamine anandamide, 2-AG, 2-araehidonoyl glycerol, MIA, monosodium iodoacetate Knee osteoarthritis (KOA), Electroacupuncture analgesia, VD-hemopressin (α)

    Received: 28 May 2024; Accepted: 16 Aug 2024.

    Copyright: © 2024 Yuan, Guo, Yi, Hou, Zhao, Wang, Jia, Baba, Li and Huo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Man Li, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
    Fu-Quan Huo, Department of Physiology and Pathophysiology, School of Basic Medicine, Xi'an Jiaotong University, Xi'an, China

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