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This experimental study investigates how lncRNA HOTTIP influences NP by examining its regulatory relationship with miR-216a-5p and downstream inflammatory signaling. A chronic constriction injury rat model and LPS-stimulated BV2 microglia are used alongside intrathecal HOTTIP-targeting lentiviral vectors and antagomiR interventions. RT-qPCR and ELISA quantify molecular targets and cytokine profiles, while binding mechanisms are tested with bioinformatics prediction, dual-luciferase reporter assays, and RNA pull-down.",{"@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/downregulation-of-lncrna-hottip-alleviates-neuropathic-pain-and-inflammation-in-chronic-constriction-injury-rats-by-targeting-mir-216a-5p/433815/",{"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/downregulation-of-lncrna-hottip-alleviates-neuropathic-pain-and-inflammation-in-chronic-constriction-injury-rats-by-targeting-mir-216a-5p/433815.png","ImageObject",300,407,{"name":92,"@type":93},"Liam","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main goal of this study on HOTTIP and neuropathic pain?","Question",{"text":112,"@type":113},"To clarify the functional role of lncRNA HOTTIP in neuropathic pain by determining how it modulates miR-216a-5p–linked inflammatory pathways.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the neuropathic pain model established and what key cell system was used?",{"text":117,"@type":113},"A chronic constriction injury (CCI) surgery was used to establish the rat NP model, and lipopolysaccharide (LPS) stimulation activated BV2 cells for inflammatory testing.",{"name":119,"@type":110,"acceptedAnswer":120},"What molecular relationship did the study identify between HOTTIP and miR-216a-5p, and what is the downstream target?",{"text":121,"@type":113},"The study found specific targeting binding between HOTTIP and miR-216a-5p, and showed that Janus kinase 2 (JAK2) is a direct target of miR-216a-5p.","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},433815,1790884549,{"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":34,"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},8796095461564,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Korean J Pain 2026;39(1):73-85 [https://doi.org/10.3344/kjp.25241](https://doi.org/10.3344/kjp.25241)[ ](https://doi.org/10.3344/kjp.25241)[pISSN 2005-9159](pISSN 2005-9159), eISSN 2093-0569  \nExperimental Research Article  \nDownregulation of lncRNA HOTTIP alleviates neuropathic pain and inflammation in chronic constriction injury rats by targeting miR-216a-5p  \nGen Zan, Riluge Wu, Yasula Ba, Gerile Sude, Runa A, and Lengge Si  \nCollege of Mongolian Medicine, Inner Mongolia Medical University, Hohhot, China  \nABSTRACT  \nBackground: Neuropathic pain (NP) is a complex and intractable chronic pain condition. This study aims to clarify the functional role of lncRNA HOTTIP in NP.  \nMethods: A chronic constriction injury (CCI) surgery was used to establish a NP rat model. Lipopolysaccharide (LPS) stimulation was employed to activate BV2 cells. Intrathecal administration of HOTTIP-targeting lentiviral vectorsand antagomiR-216a-5p was performed to lower HOTTIP and miR-216a-5p expression. RT-qPCR analyzed HOTTIP, miR-216a-5p, and inflammatory markers (cyclooxygenase-2 [COX-2], inducible nitric oxide synthase [INOS], toll-like receptor 4 [TLR4]) in rat dorsal root ganglion and BV2 cells to evaluate their roles in NP, while also tracking pain behavior changes in CCI rats to correlate molecular targets with pain perception. ELISA measured anti-inflammatory (interleukin [IL]-4) and pro-inflammatory (IL-6, tumor necrosis factor [TNF]-α) factor levels to quantify inflammation and evaluate inflammatory response severity. A specific binding relationship between HOTTIP and miR-216a-5p was evaluated using bioinformatics prediction, dual-luciferase reporter assays, and RNA pull-down techniques.  \nResults: In a rat model of CCI, inhibition of HOTTIP attenuated NP, decreased pro-inflammatory mediators (TNF-α, IL-6, COX-2, INOS, TLR4), and increased IL-4 . In LPS-induced BV2 cells, inhibition of HOTTIP also exhibited antiinflammatory effects. HOTTIP targeted binding to miR-216a-5p. Inhibition of miR-216a-5p significantly counteracted the inhibitory effects of silencing HOTTIP on NP and neuroinflammatory responses. In addition, Janus kinase 2 (JAK2) was found to be a direct target of miR-216a-5p.  \nConclusions: HOTTIP contributes to the worsening of NP and neuroinflammation by modulating the miR-216a-5p/ JAK2 pathway, exerting analgesic protective effects, indicating its potential as a therapeutic target for NP.  \nKeywords: Antagomirs; Interleukin-6; Janus Kinase 2; MicroRNAs; Neuralgia; Neuroinflammatory Disease; RNA, Long Noncoding; Toll-Like Receptor 4.  \nReceived June 30, 2025; Revised August 22, 2025; Accepted August 24, 2025 Handling Editor: Rafael Taeho Han  \nCorrespondence: Lengge Si  \nCollege of Mongolian Medicine, Inner Mongolia Medical University, No 5, Xinhua Street, Huimin District, Hohhot 010110, Inner Mongolia Autonomous Region, China  \nTel: +86-0471-6657619, Fax: +86-0471-6657619, E-mail: [silengge1987@163.com](silengge1987@163.com)  \nRuna A  \nCollege of Mongolian Medicine, Inner Mongolia Medical University, No 5, Xinhua Street, Huimin District, Hohhot 010110, Inner Mongolia Autonomous Region, China  \nTel: +86-0471-6657619, Fax: +86-0471-6657619, [E-mail:](E-mail: Aruna_arn@163.com)[ Aruna_arn@163.com](E-mail: Aruna_arn@163.com)  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by-nc/4.0](licenses/by-nc/4.0)), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.  \nCopyright © The Korean Pain Society  \nINTRODUCTION  \nNeuropathic pain (NP) is a chronic pain disorder that results directly from injury or dysfunction of the somatosensory nervous system [1] . This particular type of pain can be triggered by a variety of pathological factors, such as metabolic abnormalities (e.g., diabe","cbCaicfjQMb7ZLss","https://ap.wps.com/l/cbCaicfjQMb7ZLss","pdf",3374188,13,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction\n## Rationale for studying NP mechanisms\n## Role of non-coding RNAs and HOTTIP\n## Role of miR-216a-5p and inflammation signaling","[{\"question\":\"What is the main goal of this study on HOTTIP and neuropathic pain?\",\"answer\":\"To clarify the functional role of lncRNA HOTTIP in neuropathic pain by determining how it modulates miR-216a-5p–linked inflammatory pathways.\"},{\"question\":\"How was the neuropathic pain model established and what key cell system was used?\",\"answer\":\"A chronic constriction injury (CCI) surgery was used to establish the rat NP model, and lipopolysaccharide (LPS) stimulation activated BV2 cells for inflammatory testing.\"},{\"question\":\"What molecular relationship did the study identify between HOTTIP and miR-216a-5p, and what is the downstream target?\",\"answer\":\"The study found specific targeting binding between HOTTIP and miR-216a-5p, and showed that Janus kinase 2 (JAK2) is a direct target of miR-216a-5p.\"}]","Downregulation of lncRNA HOTTIP alleviates neuropathic pain and inflammation in chronic constriction injury rats by targeting miR-216a-5p | PDF",1790665598,33]