[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-465474-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-465474-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","tooth-pulp-afferents-and-transient-receptor-potential-trp-ion-channels-as-key-regulators-of-pulp-homeostasis-inflammation-and-pain","Tooth Pulp Afferents and Transient Receptor Potential (TRP) Ion Channels as Key Regulators of Pulp Homeostasis, Inflammation, and Pain","","Dental pain often results from compromised tooth pulp integrity caused by dental injury or caries. The dentin–pulp complex underpins dental pain biology, with trigeminal ganglion afferents innervating pulp and losing myelination at peripheral dentin. Pulpal afferents integrate thermal, chemical, and hydrodynamic inputs to drive nociception and maintain homeostasis. TRP ion channels in neurons and odontoblasts, alongside mechanosensitive channels like Piezo, form a regulatory hub. TRPV1 triggers nociception and CGRP release, TRPC5 supports cold pain, and TRPM8 responds to hyperosmotic stimuli. Pulpitis elevates TRPV1 and TRPA1 agonists, and inflammatory mediators sensitize TRP channels, amplifying pain, while CGRP promotes immune recruitment, bacterial clearance, and reparative dentinogenesis; TRP roles in these processes remain to clarify. Future work should use multi-omics and in vivo or organotypic tooth models to define TRP contributions to pain, immune responses, and regeneration, enabling new analgesic and regenerative strategies in dentistry.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/tooth-pulp-afferents-and-transient-receptor-potential-trp-ion-channels-as-key-regulators-of-pulp-homeostasis-inflammation-and-pain/465474/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/tooth-pulp-afferents-and-transient-receptor-potential-trp-ion-channels-as-key-regulators-of-pulp-homeostasis-inflammation-and-pain/465474.png","ImageObject",300,407,{"name":42,"@type":43},"Connor ","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-04","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":33},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"How do TRP ion channels contribute to tooth pulp nociception and homeostasis?","Question",{"text":62,"@type":63},"TRP channels in neurons and odontoblasts sense thermal, chemical, and hydrodynamic stimuli and help regulate both normal pulp physiology and pathological pain states, supporting pulp homeostasis and nociception.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"What specific roles do TRPV1, TRPC5, and TRPM8 play in pain modalities?",{"text":67,"@type":63},"TRPV1 mediates nociception and CGRP release, TRPC5 mediates cold pain, and TRPM8 mediates the transduction of hyperosmotic stimuli.",{"name":69,"@type":60,"acceptedAnswer":70},"How does pulpitis change TRP signaling and pain outcomes?",{"text":71,"@type":63},"Pulpitis elevates endogenous TRPV1 and TRPA1 agonists, and inflammatory mediators sensitize TRP channels, amplifying pain. CGRP then recruits immune cells, promotes bacterial clearance, and supports reparative dentinogenesis, though TRP involvement in these processes remains unclear.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},465474,1790845402,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":33,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},687207022233,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Review  \nTooth Pulp Afferents and Transient Receptor Potential (TRP) Ion Channels as Key Regulators of Pulp Homeostasis, Inflammation, and Pain  \nMan-Kyo Chung 1,2, *, Swarnalakshmi Raman 1,2 and Arpad Szallasi 3, *  \nAcademic Editor: Irmgard Tegeder  \nReceived: 16 October 2025  \nRevised: 18 December 2025  \nAccepted: 22 December 2025  \nPublished: 23 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Department of Neural and Pain Sciences, School of Dentistry, University of Maryland Baltimore, Baltimore, MD 21201, USA; [sraman1@umaryland.edu](sraman1@umaryland.edu)  \n2 UM Center to Advance Chronic Pain Research, University of Maryland Baltimore, Baltimore, MD 21201, USA  \n3 Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary  \n* [Correspondence: mchung@umaryland.edu](Correspondence: mchung@umaryland.edu) (M.-K.C.); [szallasi.arpad@semmelweis.hu](szallasi.arpad@semmelweis.hu) (A.S.)  \nAbstract  \nDental pain often arises from the compromised integrity of the tooth pulp due to dental injury or caries. The dentin–pulp complex has long been considered to be central to the unique biology of dental pain. Most trigeminal ganglion afferents projecting into tooth pulp are myelinated neurons, which lose their myelination at the site of peripheral dentin innervation. The pulpal afferents likely combine multiple internal and external stimuli to mediate nociception and maintain pulp homeostasis. Transient receptor potential (TRP) ion channels in neurons and odontoblasts, along with mechanosensitive ion channels such as Piezo, form a key molecular hub for pulpal nociception by sensing thermal, chemical, and hydrodynamic stimuli. Among these, TRP vanilloid 1 (TRPV1) mediates nociception and the release of calcitonin-gene-related peptides (CGRPs), while TRP canonical 5 (TRPC5) mediates cold pain. TRP melastatin 8 (TRPM8) mediates the transduction of hyperosmotic stimuli. Pulpitis elevates endogenous TRPV1 and TRPA1 agonists, while inflammatory mediators sensitize TRP channels, amplifying pain. CGRP recruits immune cells and promotes bacterial clearance and reparative dentinogenesis, yet the roles of TRP channels in these processes remain unclear. Future studies should use advanced multi-omics and in vivoor organotypic models in animal and human teeth to define TRP channel contributions topain, immune responses, and regeneration. Understanding neuronal and non-neuronal TRP channel interactions and their integration with other ion channels may enable novel analgesic and regenerative strategies in dentistry.  \nKeywords: transient receptor potential (TRP) channels; dental pain; tooth pulp; odontoblasts; pulpitis; TRPV1; TRPA1; pulp homeostasis  \n1. Introduction  \nTooth pain is a defining symptom of many dental pathologies that significantly affect patient quality of life. Dental pain, commonly originating from the dental pulp, can vary from short-lived stimulus-evoked discomfort to chronic spontaneous pain. Globally, the overall prevalence of tooth pain in adults is 24%[1] . Persistent dental pain interferes with eating, sleeping, and daily functioning. Such pain is strongly associated with conditions such as pulpitis and dentinal hypersensitivity. The dentin–pulp complex is innervated by specialized trigeminal sensory afferents capable of detecting subtle mechanical, thermal,  \nand chemical cues. The molecular and cellular mechanisms of intradental sensations are increasingly understood to involve not only neuronal architecture but also neuronal interactions with immune and non-neuronal cells within the pulp tissue. Among the sensory mediators, transient receptor potential (TRP) channels have emerged as pivotal in translating these stimuli into neural signals (for recent reviews, see [2–5]) .  \nTRP channels, including transien","cbCainlBhhJjhT6J","https://ap.wps.com/l/cbCainlBhhJjhT6J","pdf",2246207,39,"English","# Abstract\n# Introduction\n## Scope of the Review: Peripheral Mechanisms Related to Pain Originating from Dental Pulp","[{\"question\":\"How do TRP ion channels contribute to tooth pulp nociception and homeostasis?\",\"answer\":\"TRP channels in neurons and odontoblasts sense thermal, chemical, and hydrodynamic stimuli and help regulate both normal pulp physiology and pathological pain states, supporting pulp homeostasis and nociception.\"},{\"question\":\"What specific roles do TRPV1, TRPC5, and TRPM8 play in pain modalities?\",\"answer\":\"TRPV1 mediates nociception and CGRP release, TRPC5 mediates cold pain, and TRPM8 mediates the transduction of hyperosmotic stimuli.\"},{\"question\":\"How does pulpitis change TRP signaling and pain outcomes?\",\"answer\":\"Pulpitis elevates endogenous TRPV1 and TRPA1 agonists, and inflammatory mediators sensitize TRP channels, amplifying pain. CGRP then recruits immune cells, promotes bacterial clearance, and supports reparative dentinogenesis, though TRP involvement in these processes remains unclear.\"}]","Tooth Pulp Afferents and Transient Receptor Potential (TRP) Ion Channels as Key Regulators of Pulp Homeostasis, Inflammation, and Pain | PDF",1790769669,98]