[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-435664-105":59,"doc-detail-435664-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","aptamer-guided-rna-nanocarriers-for-receptor-level-targeting-of-cgrp-pathways-in-chronic-migraine-letter-to-the-editor","Aptamer-guided RNA nanocarriers for receptor-level targeting of CGRP pathways in chronic migraine - Letter to the Editor","","Migraine is a disabling neurovascular disorder driven by trigeminovascular overactivation and chronic sensitization, with dysfunction of the calcitonin gene-related peptide (CGRP) pathway sustaining pain and related symptoms. Current therapies, including monoclonal antibodies and small gepants, improve outcomes but face cost, limited response, systemic adverse effects, and breakthrough headaches. Aptamer-guided RNA nanocarriers are proposed to deliver RNA interference and suppress CGRP receptor signaling with receptor-level precision while addressing preclinical efficacy and translational challenges.",{"@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/aptamer-guided-rna-nanocarriers-for-receptor-level-targeting-of-cgrp-pathways-in-chronic-migraine-letter-to-the-editor/435664/",{"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/aptamer-guided-rna-nanocarriers-for-receptor-level-targeting-of-cgrp-pathways-in-chronic-migraine-letter-to-the-editor/435664.png","ImageObject",300,407,{"name":92,"@type":93},"hdkawk","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",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is CGRP pathway targeting important in chronic migraine?","Question",{"text":113,"@type":114},"CGRP pathway dysfunction promotes persistent pain and related symptoms, and current therapies that modulate this axis still leave limitations such as cost, limited response, systemic adverse effects, and breakthrough headaches.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How do aptamer-guided RNA nanocarriers aim to improve specificity?",{"text":118,"@type":114},"Aptamers bind cell surface receptors with high affinity, and coupling them to RNA nanocarriers enables direct delivery of microRNAs or siRNAs to CGRP receptor-expressing neurons for receptor-level targeting and minimal off-target effects.",{"name":120,"@type":111,"acceptedAnswer":121},"What major challenges could prevent clinical adoption of these technologies?",{"text":122,"@type":114},"Evidence is limited beyond in vitro and early in vivo models, and aptamer–RNA complex stability, pharmacokinetics, and immunogenicity require standardization. Manufacturing costs, inconsistent nanoparticle reporting, hepatotoxicity signals, and uncertain long-term safety also remain concerns.","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},435664,1791116562,{"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":14,"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":24,"preview_page_count":4},3985747859855,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Letter to the Editor  \nAptamer-guided RNA nanocarriers for receptor-level targeting of CGRP pathways in chronic migraine  \nFahad Amin, MBBSa , Muhammad Hassan Asif, MBBSb , Raghabendra Kumar Mahato, MBBSc ,*  \nTo the Editor,  \nMigraine is a disabling neurovascular disorder that is characterized by recurrent headaches. It is mainly caused by overactivation of the trigeminovascular system and chronic sensitization. Pathophysiology of migraine involves dysfunction of the calcitonin gene-related peptide (CGRP) pathway that promotes persistent pain and other symptoms. Although the current therapies, such as monoclonal antibodies and small gepant molecules, have markedly improved clinical outcomes, limitations still remain. These include high costs, low response rates, systemic adverse effects, and breakthrough headaches[1]. Thus, there remains an unmet need for targeted molecular therapies that can silence CGRP activity in a cellspecific manner.  \nAptamer-guided RNA nanocarriers represent an emerging modality that may address these limitations. Aptamers are small nucleic acid ligands that bind with high affinity to cell surface receptors. By coupling aptamers to RNA nanocarriers, we can deliver microRNAs, antisense RNAs, or siRNAs directly to specific CGRP receptor-expressing neurons (e.g., trigeminal ganglion and meningealneurosusceptorsin this case). These nanocarriers demonstrate receptor-level targeting gives millimeter-scale precision and minimal off-target side effects[2]. Moreover, they can downregulate the expression of the CGRP receptor, ligand and downstream molecules involved in neuronal inflammation.  \nPreclinical studies in this context have yielded promising results. Studies have shown that aptamers facilitate the transport of nucleic acids across the blood–brain barrier. In this way, it may allow us to achieve therapeutic drug levels in the target tissues reliably. In a nitroglycerin-induced chronic migraine model,  \naFaculty of Medicine, King Edward Medical University, Lahore, Pakistan, bDepartment of Medicine, King Edward Medical University, Lahore, Pakistan and cDepartment of Medicine, Gandaki Medical College Teaching Hospital and Research Centre, Pokhara, Nepal  \nSponsorships or competing interests that may be relevant to content are disclosed at the end of this article.  \n*Corresponding author. Address: Department of Medicine, Gandaki Medical College Teaching Hospital and Research Centre, Pokhara 33700, Nepal. Tel.: +[977 9745829807. E-mail:102raghabendrakumarmahato@gmail.com](977 9745829807. E-mail:102raghabendrakumarmahato@gmail.com)[ ](977 9745829807. E-mail:102raghabendrakumarmahato@gmail.com)(R.K. Mahato).  \nCopyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.  \nAnnals of Medicine & Surgery (2026) 88:1114–1115  \nReceived 18 November 2025; Accepted 24 November 2025  \nPublished online 9 December 2025  \n[http://dx.doi.org/10.1097/MS9.0000000000004513](http://dx.doi.org/10.1097/MS9.0000000000004513)  \nintrathecal administration of siRNA significantly reduced the expression of phosphorylated CGRP in trigeminovascular tissues[3] . Another study demonstrated that L-RNA complexes bind CGRP and reduce neuronal firing in the rat spinal trigeminal nucleus in response to meningeal stimulus[4] . Taken together, these early data support the concept that combining receptor-targeted aptamers with RNA interference could enable highly specific, mechanistically rational suppression of CGRP-driven neuroinflammation in chronic migraine.  \nHowever, several challenges must be acknowledged before these technologies can be considered clinically viable. First, there are no robust human ","cbCaidOy0qMj963u","https://ap.wps.com/l/cbCaidOy0qMj963u","pdf",164009,"English","# Letter to the Editor\n## Background: migraine pathology and unmet needs\n## Rationale: aptamer-guided RNA nanocarriers\n## Preclinical evidence and potential mechanisms\n## Translational challenges and safety considerations\n## Conclusion and clinical outlook\n## TITAN disclosure and ethics","[{\"question\":\"Why is CGRP pathway targeting important in chronic migraine?\",\"answer\":\"CGRP pathway dysfunction promotes persistent pain and related symptoms, and current therapies that modulate this axis still leave limitations such as cost, limited response, systemic adverse effects, and breakthrough headaches.\"},{\"question\":\"How do aptamer-guided RNA nanocarriers aim to improve specificity?\",\"answer\":\"Aptamers bind cell surface receptors with high affinity, and coupling them to RNA nanocarriers enables direct delivery of microRNAs or siRNAs to CGRP receptor-expressing neurons for receptor-level targeting and minimal off-target effects.\"},{\"question\":\"What major challenges could prevent clinical adoption of these technologies?\",\"answer\":\"Evidence is limited beyond in vitro and early in vivo models, and aptamer–RNA complex stability, pharmacokinetics, and immunogenicity require standardization. Manufacturing costs, inconsistent nanoparticle reporting, hepatotoxicity signals, and uncertain long-term safety also remain concerns.\"}]","Aptamer-guided RNA nanocarriers for receptor-level targeting of CGRP pathways in chronic migraine - Letter to the Editor | PDF",1790674684]