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Methods: Pain hypersensitivity was assessed after single intrathecal (i.t.) trehalose-6,6'-dibehenate (TDB) doses (0.1, 1, 10 µg) or repeated i.t. injections (10 µg/day for 2 days, R-TDB), compared with SNL. Spinal microglia (Iba1) and astrocytes (GFAP) were analyzed. Results: Single and repeated TDB induced significant, dose-independent hypersensitivity; R-TDB yielded greater mechanical allodynia, while thermal effects resembled SNL. Microglia and astrocyte activation occurred faster with R-TDB. Conclusions: Spinal Mincle receptor activation induces persistent neuropathic pain-like hypersensitivity without peripheral nerve injury, with a more rapid neuroinflammatory response than SNL.",{"@graph":69,"@context":123},[70,84,106],{"@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/spinal-mincle-activation-as-a-new-model-of-neuroinflammation-associated-neuropathic-pain-comparison-with-spinal-nerve-ligation/433830/",{"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/spinal-mincle-activation-as-a-new-model-of-neuroinflammation-associated-neuropathic-pain-comparison-with-spinal-nerve-ligation/433830.png","ImageObject",300,407,{"name":92,"@type":93},"Liam","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",18,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What models were compared in this study?","Question",{"text":113,"@type":114},"The study compared spinal nerve ligation (SNL) with spinal Mincle activation using intrathecal TDB (single injection or repeated injections).","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was pain hypersensitivity evaluated and for how long?",{"text":118,"@type":114},"Pain hypersensitivity was assessed after intrathecal TDB or SNL, and pain behaviors were evaluated over 28 days.",{"name":120,"@type":111,"acceptedAnswer":121},"Did TDB show dose-dependent effects in inducing hypersensitivity?",{"text":122,"@type":114},"Intrathecal TDB at all tested doses produced significant pain hypersensitivity from day 1 to day 28, with no clear dose-dependent effects.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},433830,1791034849,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"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):96-105 [https://doi.org/10.3344/kjp.25299](https://doi.org/10.3344/kjp.25299)[ ](https://doi.org/10.3344/kjp.25299)[pISSN 2005-9159](pISSN 2005-9159), eISSN 2093-0569  \nExperimental Research Article  \nSpinal Mincle activation as a new model of neuroinflammation-associated neuropathic pain:  \ncomparison with spinal nerve ligation  \nJihoon Yang1, Woong Mo Kim1,2, Seongtae Jeong1,2, Hong Beom Bae1,2, and Jeong Il Choi1,2  \n1 Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Gwangju, Korea  \n2 Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea  \nABSTRACT  \nBackground: The spinal nerve ligation (SNL) model induces neuropathic pain through peripheral nerve injury, leading to central sensitization and neuroinflammation. Recent evidence suggests that activation of Mincle (macrophage-inducible C-type lectin) in the spinal cord may also trigger pain hypersensitivity without peripheral nerve injury. This study compared the effects of SNL and spinal Mincle activation on pain behavior and neuroglial activation.  \nMethods: Pain hypersensitivity was evaluated following a single intrathecal (i.t.) injection of the Mincle ligand, trehalose-6,6'-dibehenate (TDB) at doses of 0.1 µg, 1 µg, or 10 µg (single injection, S-TDB) . In a separate group, rats received repeated i.t. TDB injection (10 µg/day for 2 days, R-TDB) or surgery for SNL. Pain behaviors were assessed for 28 days. Spinal expression of microglia (Iba1) and astrocytes (GFAP) was analyzed via immunofluorescence in R-TDB and SNL groups.  \nResults: I.t. TDB administration at all tested doses produced significant pain hypersensitivity from day 1 to day 28, with no clear dose-dependent effects. Repeated i.t. TDB administration led to greater mechanical allodynia than S-TDB, but thermal responses were similar. Compared to SNL, the R-TDB group produced a comparable pain hypersensitivity to SNL but exhibited faster activation of microglia and astrocytes.  \nConclusions: Spinal Mincle receptor activation via i.t. TDB induces persistent pain hypersensitivity in the absence of peripheral nerve injury, accompanied by a more rapid neuroinflammatory response than that observed in the SNL model. These findings support Mincle activation as a potential experimental model for neuroinflammationassociated neuropathic pain.  \nKeywords: Astrocyte; Central Nervous System Sensitization; Hyperalgesia; Lectins, C-Type; Microglia; Neuroinflammatory Disease; Peripheral Nerve Injuries.  \nINTRODUCTION  \nCentral sensitization is considered a key mechanism  \nunderlying the development and maintenance of neuropathic pain and is primarily associated with neuroinflammation in the central nervous system (CNS) [1] . During  \nReceived August 13, 2025; Revised September 21, 2025; Accepted October 1, 2025 Handling Editor: Sang Hun Kim  \nCorrespondence: Jeong Il Choi  \nDepartment of Anesthesiology and Pain Medicine, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea  \nTel: +82-62-220-6893, Fax: +82-62-232-6294, [E-mail:](E-mail: jichoi@jnu.ac.kr)[ jichoi@jnu.ac.kr](E-mail: jichoi@jnu.ac.kr)  \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  \nthe process of neuroinflammation, activated microglia and astrocytes release various inflammatory mediators that promote central sensitization, thereby excessively amplifying pain signal transmission and contributing to the persistence of chronic pain [2] . Recently, central sensitization driven by neuroinflammation is suggested asan important mechanism for c","cbCaivx7gJb32IsN","https://ap.wps.com/l/cbCaivx7gJb32IsN","pdf",8616358,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What models were compared in this study?\",\"answer\":\"The study compared spinal nerve ligation (SNL) with spinal Mincle activation using intrathecal TDB (single injection or repeated injections).\"},{\"question\":\"How was pain hypersensitivity evaluated and for how long?\",\"answer\":\"Pain hypersensitivity was assessed after intrathecal TDB or SNL, and pain behaviors were evaluated over 28 days.\"},{\"question\":\"Did TDB show dose-dependent effects in inducing hypersensitivity?\",\"answer\":\"Intrathecal TDB at all tested doses produced significant pain hypersensitivity from day 1 to day 28, with no clear dose-dependent effects.\"}]","Spinal Mincle activation as a new model of neuroinflammation-associated neuropathic pain - comparison with spinal nerve ligation | PDF",1790665644,25]