Identification of sensory fiber types in mouse temporomandibular joint tissues
Temporomandibular joint (TMJ) disorders (TMJDs) are linked to heightened nerve sensitivity in TMJ tissues. To set the groundwork for investigating the mechanisms governing this increased responsiveness, this study aimed to identify the types of nerves in the retrodiscal tissue (retrodisc), anterior disc, and joint capsule of mouse TMJ using immunohistochemistry (IHC) and reporter mice. The pan-sensory neuronal marker pgp9.5 revealed no nerves in the articular disc but identified approximately 70% unmyelinated and 30% myelinated fibers in other TMJ tissues. Nearly all sensory fibers in the joint capsule and anterior disc were CGRP<sup>+</sup> peptidergic fibers, while the retrodisc contained about 80% peptidergic fibers. Notably, CGRP<sup>-</sup>/NFH<sup>+</sup> myelinated non-peptidergic nerves were absent, indicating the absence of non-nociceptive fibers (A-LTMRs) in TMJ tissues. Almost all sensory fibers in the joint capsule and anterior disc were Htr3a<sup>+</sup>, with the retrodisc containing 60-70% Htr3a<sup>+</sup> fibers. Additionally, TMJ tissues had minimal to no (< 5%) MrgprD<sup>+</sup>, MrgprA3<sup>+</sup>, MrgprC11<sup>+</sup>, somatostatin<sup>+</sup>, or parvalbumin<sup>+</sup> fibers, except for the retrodisc, which had about 20% Mrgpr<sup>+</sup> fibers. Excluding articular discs, TMJ tissues were highly vascularized, with blood vessels surrounded by both sensory and sympathetic (TH<sup>+</sup>) nerves. Overall, TMJ tissues were predominantly innervated by peptidergic fibers, with a minor presence of other non-peptidergic fibers.
Authors
- Alia M. Obeidat (ORCID: https://orcid.org/0000-0002-3522-0084)
- Yi Zou (ORCID: https://orcid.org/0000-0002-1742-9650)
- Michael J. Iadarola (ORCID: https://orcid.org/0000-0001-7188-9810)
- Oscar A. Ruíz (ORCID: https://orcid.org/0000-0001-6387-6227)
- Tristan Maerz (ORCID: https://orcid.org/0000-0002-4523-6012)
- Yona Levites (ORCID: https://orcid.org/0000-0001-6925-4525)
- Malin Ernberg (ORCID: https://orcid.org/0000-0003-4152-5439)
- Spencer Fullam (ORCID: https://orcid.org/0000-0001-9012-3802)
- Russell Ray (ORCID: https://orcid.org/0000-0001-9610-2703)
- Lindsey J. Macpherson (ORCID: https://orcid.org/0000-0002-1089-3733)
- Racel Cela
- Zhao Lai (ORCID: https://orcid.org/0000-0002-3543-5376)
- Nele A Haelterman (ORCID: https://orcid.org/0000-0002-1431-7581)
- Brian A. Goolsby
- Merissa Olmer (ORCID: https://orcid.org/0000-0002-2483-4216)
- Michael Strinden
- Joshua D. Stover (ORCID: https://orcid.org/0000-0001-5532-6102)
- Dawen Cai (ORCID: https://orcid.org/0000-0003-4471-2061)
- M. Danilo Boada (ORCID: https://orcid.org/0000-0002-8973-3010)
- Daniel Carpio (ORCID: https://orcid.org/0000-0001-7929-1151)
- Kevin J. Otto (ORCID: https://orcid.org/0000-0002-2317-6194)
- Laura Sánchez (ORCID: https://orcid.org/0000-0001-7927-5303)
- M. Franklin Dolwick
- Janak Gaire (ORCID: https://orcid.org/0000-0002-1862-8360)
- Jie Li (ORCID: https://orcid.org/0000-0003-0121-1291)
- Azeez Olakunle Ishola (ORCID: https://orcid.org/0000-0001-9378-7858)
- Kim C. Worley (ORCID: https://orcid.org/0000-0002-0282-1000)
- Airam Nicole Vivanco-Estela (ORCID: https://orcid.org/0009-0001-9617-9249)
- Priya Kulkarni
- Alexus Roberts
- E. Wang (ORCID: https://orcid.org/0000-0003-4644-1306)
- Lai Wang (ORCID: https://orcid.org/0000-0002-3323-7210)
- Armen N. Akopian (ORCID: https://orcid.org/0000-0002-1066-253X)
- Dongjun Ren
- Folly Patterson (ORCID: https://orcid.org/0000-0003-0613-8804)
- Joshua J. Emrick (ORCID: https://orcid.org/0000-0001-5619-1078)
- M. Silva (ORCID: https://orcid.org/0000-0001-9294-7688)
- Dana E. Orange (ORCID: https://orcid.org/0000-0001-9859-7199)
- Shad B. Smith (ORCID: https://orcid.org/0000-0002-2056-225X)
- Theodore J. Price (ORCID: https://orcid.org/0000-0002-6971-6221)
- Brendan Lee (ORCID: https://orcid.org/0000-0001-8573-4211)
- Rachel E. Miller
- Yufang Jin (ORCID: https://orcid.org/0000-0002-9049-9807)
- Benjamin Russell Arenkiel (ORCID: https://orcid.org/0000-0001-9047-2420)
- Joost Wagenaar (ORCID: https://orcid.org/0000-0003-0837-7120)
- Alexei V. Tumanov (ORCID: https://orcid.org/0000-0001-6042-0152)
- Elizabeth Ronan
- Miguel Otero (ORCID: https://orcid.org/0000-0002-4945-2994)
- Jiansen Yan
- Anita Bandrowski (ORCID: https://orcid.org/0000-0002-5497-0243)
- Maryann E. Martone (ORCID: https://orcid.org/0000-0002-8406-3871)
- Richard J. Miller (ORCID: https://orcid.org/0000-0002-8254-6714)
- Susan Tappan (ORCID: https://orcid.org/0000-0001-5120-3770)
- Alejandro J. Almarza (ORCID: https://orcid.org/0000-0003-4602-9258)
- Chris Donnelly (ORCID: https://orcid.org/0000-0002-5392-7876)
- Danielle L. Freburg-Hoffmeister
- Bruna Balbino de Paula (ORCID: https://orcid.org/0000-0003-1924-3355)
- Joshua D. Wythe (ORCID: https://orcid.org/0000-0002-3225-2937)
- Anne‐Marie Malfait
- Frank C. Ko
- Hernan Prieto
- J Alfaro (ORCID: https://orcid.org/0000-0001-5131-9175)
- Zixue Jin (ORCID: https://orcid.org/0000-0002-7857-398X)
- Kyle M. Allen (ORCID: https://orcid.org/0000-0002-2911-2538)
- Michael D. Newton (ORCID: https://orcid.org/0000-0003-1262-0613)
- Robert M. Caudle (ORCID: https://orcid.org/0000-0002-2394-4114)
- Zelong Dou
- Yangjin Bae (ORCID: https://orcid.org/0000-0003-2397-0192)
- Yenisel Cruz‐Almeida (ORCID: https://orcid.org/0000-0002-0065-0236)
- Başak Dönertaş Ayaz (ORCID: https://orcid.org/0000-0003-3829-6049)
- Martin Lotz (ORCID: https://orcid.org/0000-0002-6299-8799)
- Bella Mehta (ORCID: https://orcid.org/0000-0003-4646-1446)
- Sudhish Jayachandran
- Hannah Swahn
- Ibdanelo Cortez (ORCID: https://orcid.org/0000-0003-2495-1479)
- Akash Gandhi
- Rui Chen (ORCID: https://orcid.org/0000-0003-3728-2577)
- Yong Chen (ORCID: https://orcid.org/0000-0002-0649-0763)
- Sienna K. Perry (ORCID: https://orcid.org/0000-0003-2964-9842)
- Shingo Ishihara
- Abbas Muhammad
- Marlena Pela
- Jacqueline Boccanfuso
- S. V. Greene
- Mairobys Soccorro Gonzalez
- Jyl Boline
- Camilla Majano
- Brian S.C. Constantinescu (ORCID: https://orcid.org/0009-0008-4456-076X)
- Kaitlin M. Southern (ORCID: https://orcid.org/0009-0008-4926-9998)
- Shane H Priester
Institutions
- Northwestern University (US)
- Hospital for Special Surgery (US)
- National Institutes of Health (US)
- Scripps Institution of Oceanography (US)
- Emory University (US)
- The University of Texas at Dallas (US)
- The University of Texas at San Antonio Health Science Center (US)
- University of Pittsburgh (US)
- Duke University (US)
- Baylor College of Medicine (US)
- University of California, Irvine (US)
- University of Michigan (US)
- Karolinska Institutet (SE)
- University of Florida (US)
- University of California San Diego (US)
- Champlain Valley Union High School (US)
- Scripps (United States) (US)
- Irvine University (US)
- Integrative Health Technologies (United States) (US)
- National Institutes of Health Clinical Center (US)
- The University of Texas at San Antonio (US)
- Wake Forest University (US)
- Rush University (US)
- University of Virginia (US)
- University of Pennsylvania (US)
- Rockefeller University (US)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1038/s41598-025-17508-x
- Primary Topic
- Temporomandibular Joint Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute of Dental and Craniofacial Research