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This comprehensive review evaluates the healing potential, mechanisms of action, medical applications, and safety evidence of melittin and BVA across different musculoskeletal conditions. It addresses the clinical burden of these disorders, including pain and functional limitation, and reviews biological pathways linked to inflammation and analgesic effects. Emphasis is placed on how BVA compounds may modulate inflammatory signaling and related mediators while considering tolerability and risk records.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/bee-venom-acupuncture-in-the-treatment-of-musculoskeletal-system-disorders-a-comprehensive-review/439717/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/bee-venom-acupuncture-in-the-treatment-of-musculoskeletal-system-disorders-a-comprehensive-review/439717.png","ImageObject",300,407,{"name":92,"@type":93},"Terk","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does bee venom acupuncture (BVA) involve, and what is melittin?","Question",{"text":112,"@type":113},"BVA uses bee venom injection into specific acupuncture points. Melittin is the main constituent of bee venom and a key focus of the review’s mechanism and safety discussion.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why are musculoskeletal system disorders a major healthcare concern?",{"text":117,"@type":113},"These disorders are highly prevalent and contribute to pain, disability, and a substantial rehabilitation need worldwide. The review also notes that major categories include back and neck pain, arthritic conditions, and soft-tissue syndromes.",{"name":119,"@type":110,"acceptedAnswer":120},"How does melittin relate to inflammation-related biological pathways?",{"text":121,"@type":113},"The review links inflammatory responses to immune-cell activation and signaling pathways such as TLR4 and NF-κB. It also describes how melittin may regulate cytokine production and oxidative-stress mediators to support anti-inflammatory outcomes.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},439717,1791453360,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099525198933,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Wiley  \nPain Research and Management Volume 2025, Article ID 1766393, 13 pages [https://doi.org/10.1155/prm/1766393](https://doi.org/10.1155/prm/1766393)  \nReview Article  \nBee Venom Acupuncture in the Treatment of Musculoskeletal System Disorders: A Comprehensive Review  \nXiaodi Zou , 1,2 Yanzhao Dong, 1 Ahmad Alhaskawi , 1 Haiying Zhou,1  \nSohaib Hasan Abdullah Ezzi,3 Vishnu Goutham Kota,4  \nMohamed Hasan Abdulla Hasan Abdulla,4 Sahar Ahmed Abdalbary,5 Zhenfeng Liu,6 Changxin Wang ,2 and Hui Lu 1  \n1 Department of Orthopedics, Te First Afliated Hospital, Zhejiang University, Hangzhou City, Zhejiang Province, China 2 Department of Orthopedics, Te Second Afliated Hospital of Zhejiang Chinese Medical University, Hangzhou City,  \nZhejiang Province, China  \n3 Department of Orthopedics, Tird Xiangya Hospital, Central South University, Changsha City, Hunan Province, China 4 School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China  \n5 Department of Orthopedic Physical Terapy, Nahda University in Beni Suef, Beni Suef City,  \nBeni Suef Governorate Province, Egypt  \n6 Department of Nuclear Medicine, Te First Afliated Hospital, Zhejiang University, Hangzhou City, Zhejiang Province, China Correspondence should be addressed to Changxin Wang; wcxzcmu@163.com and Hui Lu; [huilu@zju.edu.cn](huilu@zju.edu.cn)  \nReceived 18 February 2025; Revised 29 October 2025; Accepted 13 November 2025  \nAcademic Editor: Massimiliano Valeriani  \nCopyright © 2025 Xiaodi Zou et al. Pain Research and Management published by John Wiley & Sons Ltd. Tis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \nDisorders of the musculoskeletal system cover a broad spectrum of conditions that impact the muscles, skeletal structure, joints, tendons, and ligaments, leading to discomfort, swelling, and limited movement. Bee venom acupuncture (BVA), a practice commonly used in Asian countries, has been employed for a considerable time in traditional medicine systems to treat these disorders by utilizing bee venom and its main constituent, melittin. Te purpose of this extensive evaluation on is to ofera detailed examination of the healing capabilities, modes of operation medical uses, and safety records of melittin and BVA in the treatment of diferent musculoskeletal disorders.  \nKeywords: bee venom acupuncture; complementary therapies; melittin; musculoskeletal disorders; pain management  \n1. Introduction  \nTe high occurrence and resulting pain and disability of musculoskeletal disorders place a substantial strain on healthcare systems worldwide [1].Tese disorders may be congenital and acquired and may include deformities, amputations, or other abnormalities. Musculoskeletal disorders primarily consist of back and neck pain disorders, arthritic conditions, and soft tissues syndromes afecting the tendons, ligaments, muscles, and cartilages [1] .  \nIndustrialized nations have a particularly high prevalence of musculoskeletal disorders, which are the primary  \ncause of pain and disability worldwide [1–4] . As per the WHO report, they also make up the largest proportion of individuals requiring rehabilitation worldwide, constituting around 66% of all adults in need of rehabilitations. NSAIDs, such as naproxen, ibuprofen, and diclofenac, are the most frequently prescribed medicines for musculoskeletal disorders [5] . So far, only a limited number of therapy options have been developed [6] . Bee venom acupuncture (BVA), a traditional Asian medical practice primarily from Korea and China, utilizes bee venom injection into specifc acupuncture points to treat arthritis, alleviate pain, and address rheumatoid diseases [7, 8](Figure 1) .  \n2 Pain Research and Management  \nTLR4  \nIκB  \nNF-κB  \nP38  \nNEMO  \nERK1/2  \nAKT PLCγ1  \nNucleus  \nMelittin  \nCell Membrane  \nPDGFRβ  \nproinflammatory gene expression  \nIL-6  \nIL-1β ","cbCailqqC23sPNxz","https://ap.wps.com/l/cbCailqqC23sPNxz","pdf",1183708,13,"English","# Introduction\n## Musculoskeletal disorders burden and current therapies\n## Bee venom acupuncture and melittin background\n# Pain Research and Management\n## Graphical abstract\n# Mechanisms\n## Immune cell migration and TLR4/NF-κB signaling\n## Oxidative stress and ROS modulation\n## Cytokine regulation by melittin","[{\"question\":\"What does bee venom acupuncture (BVA) involve, and what is melittin?\",\"answer\":\"BVA uses bee venom injection into specific acupuncture points. Melittin is the main constituent of bee venom and a key focus of the review’s mechanism and safety discussion.\"},{\"question\":\"Why are musculoskeletal system disorders a major healthcare concern?\",\"answer\":\"These disorders are highly prevalent and contribute to pain, disability, and a substantial rehabilitation need worldwide. The review also notes that major categories include back and neck pain, arthritic conditions, and soft-tissue syndromes.\"},{\"question\":\"How does melittin relate to inflammation-related biological pathways?\",\"answer\":\"The review links inflammatory responses to immune-cell activation and signaling pathways such as TLR4 and NF-κB. It also describes how melittin may regulate cytokine production and oxidative-stress mediators to support anti-inflammatory outcomes.\"}]","Bee Venom Acupuncture in the Treatment of Musculoskeletal System Disorders - A Comprehensive Review | PDF",1790690003,33]