{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:34:03Z","timestamp":1791912843462,"version":"4.3.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>Multiple sensory afferents, including mechanosensitive and nociceptive nerves, are projected to the periodontium. Peptidergic afferents expressing transient receptor potential vanilloid 1 (TRPV1), a receptor for capsaicin, mediate pain caused by orthodontic forces. However, their role in orthodontic force-induced alveolar bone remodeling is poorly understood as is the contribution of mechanosensitive ion channels such as Piezo2 in nociceptive nerves. To investigate this role, we studied orthodontic tooth movement and alveolar bone remodeling using neural manipulations and genetic mouse models. Chemical ablation of TRPV1-expressing afferents localized to the trigeminal ganglia decreased orthodontic force\u2013induced tooth movement and the number of osteoclasts in alveolar bone on the compression side. The extent of the force-induced increase in the ratio of receptor activator of nuclear factor kappa-B ligand\/osteoprotegerin in the periodontium was modestly decreased in the chemical ablation group. Furthermore, chemogenetic silencing of TRPV1-lineage afferents reduced orthodontic tooth movement and the number of osteoclasts. Piezo2 was expressed in most periodontal afferents, and chemogenetic inhibition of Piezo2-expressing neurons decreased orthodontic tooth movement and the number of osteoclasts. In addition, the conditional knockout of Piezo2 in TRPV1-lineage afferents decreased orthodontic tooth movement and the number of osteoclasts. Overall, these results suggest that nociceptor neurons play critical roles in orthodontic force\u2013induced alveolar bone remodeling and that the mechanical activation of neuronal Piezo2 in nociceptive nerves facilitates orthodontic tooth movement and associated alveolar bone remodeling.<\/jats:p>","DOI":"10.1177\/00220345251317429","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:34:16Z","timestamp":1741754056000},"page":"890-899","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Nociceptor Neurons Facilitate Orthodontic Tooth Movement via Piezo2 in Mice"],"prefix":"10.1177","volume":"104","author":[{"given":"S.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neural and Pain Sciences, School of Dentistry, University of Maryland Baltimore. Center to Advance Chronic Pain Research, Baltimore, MD, USA"},{"name":"Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Neural and Pain Sciences, School of Dentistry, University of Maryland Baltimore. Center to Advance Chronic Pain Research, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Parastooei","sequence":"additional","affiliation":[{"name":"Department of Neural and Pain Sciences, School of Dentistry, University of Maryland Baltimore. Center to Advance Chronic Pain Research, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Kumari","sequence":"additional","affiliation":[{"name":"Department of Neural and Pain Sciences, School of Dentistry, University of Maryland Baltimore. Center to Advance Chronic Pain Research, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7814-7342","authenticated-orcid":false,"given":"Y.","family":"Abbasi","sequence":"additional","affiliation":[{"name":"Department of Neural and Pain Sciences, School of Dentistry, University of Maryland Baltimore. Center to Advance Chronic Pain Research, Baltimore, MD, USA"},{"name":"Program in Dental Biomedical Sciences, University of Maryland Baltimore, School of Dentistry, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Elnabawi","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Maryland Baltimore, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.-K.","family":"Pae","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Maryland Baltimore, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.C.","family":"Ko","sequence":"additional","affiliation":[{"name":"Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7637-1148","authenticated-orcid":false,"given":"M.-K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Neural and Pain Sciences, School of Dentistry, University of Maryland Baltimore. Center to Advance Chronic Pain Research, Baltimore, MD, USA"},{"name":"Program in Dental Biomedical Sciences, University of Maryland Baltimore, School of Dentistry, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-023-00774-x"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2018.05.026"},{"key":"e_1_3_3_4_1","doi-asserted-by":"crossref","unstructured":"Arora V Campbell JN Chung MK. 2021. Fight fire with fire: neurobiology of capsaicin-induced analgesia for chronic pain. Pharmacol Ther. 220:107743. https:\/\/doi.org\/10.1016\/j.pharmthera.2020.107743.","DOI":"10.1016\/j.pharmthera.2020.107743"},{"key":"e_1_3_3_5_1","doi-asserted-by":"crossref","unstructured":"Austah ON Lillis KV Akopian AN Harris SE Grinceviciute R Diogenes A. 2022. Trigeminal neurons control immune-bone cell interaction and metabolism in apical periodontitis. Cell Mol Life Sci. 79(6):330. https:\/\/doi.org\/10.1007\/s00018-022-04335-w.","DOI":"10.1007\/s00018-022-04335-w"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2008.08.016"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/2151237X.2007.10129236"},{"key":"e_1_3_3_8_1","doi-asserted-by":"crossref","unstructured":"Brakspear KS Mason DJ. 2012. Glutamate signaling in bone. Front Endocrinol. 3:97. https:\/\/doi.org\/10.3389\/fendo.2012.00097.","DOI":"10.3389\/fendo.2012.00097"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902310408"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345211016285"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-0265-3_33"},{"key":"e_1_3_3_12_1","doi-asserted-by":"crossref","unstructured":"Chung MK Wang S Oh SL Kim YS. 2021. Acute and chronic pain from facial skin and oral mucosa: Unique neurobiology and challenging treatment. Int J Mol Sci. 22(11):5810. https:\/\/doi.org\/10.3390\/ijms22115810.","DOI":"10.3390\/ijms22115810"},{"key":"e_1_3_3_13_1","doi-asserted-by":"crossref","unstructured":"Du Y Yang K. 2023. Role of mechanosensitive ion channel Piezo1 in tension-side orthodontic alveolar bone remodeling in rats. Arch Oral Biol. 155:105798. https:\/\/doi.org\/10.1016\/j.archoralbio.2023.105798.","DOI":"10.1016\/j.archoralbio.2023.105798"},{"key":"e_1_3_3_14_1","doi-asserted-by":"crossref","unstructured":"El-Angbawi A McIntyre G Fleming PS Bearn D. 2023. Non-surgical adjunctive interventions for accelerating tooth movement in patients undergoing orthodontic treatment. Cochrane Database Syst Rev. 6(6):CD010887. https:\/\/doi.org\/10.1002\/14651858.cd010887.pub3.","DOI":"10.1002\/14651858.CD010887.pub3"},{"key":"e_1_3_3_15_1","doi-asserted-by":"crossref","unstructured":"Guo R Zhou Y Long H Shan D Wen J Hu H Yang H Wu Z Lai W. 2019. Transient receptor potential vanilloid 1-based gene therapy alleviates orthodontic pain in rats. Int J Oral Sci. 11(1):11. https:\/\/doi.org\/10.1038\/s41368-019-0044-3.","DOI":"10.1038\/s41368-019-0044-3"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-3623(97)00078-5"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2023.10.020"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2017.10.017"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejo\/cjab072"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kjms.2018.01.007"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijos.2016.24"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.19"},{"key":"e_1_3_3_23_1","doi-asserted-by":"crossref","unstructured":"Murthy SE Loud MC Daou I Marshall KL Schwaller F Kuhnemund J Francisco AG Keenan WT Dubin AE Lewin GR et al. 2018. The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain in mice. Sci Transl Med. 10(462):eaat9897. https:\/\/doi.org\/10.1126\/scitranslmed.aat9897.","DOI":"10.1126\/scitranslmed.aat9897"},{"key":"e_1_3_3_24_1","doi-asserted-by":"crossref","unstructured":"Nie X Abbasi Y Chung MK. 2024. Piezo1 and Piezo2 collectively regulate jawbone development. Development. 151(9):dev202386. https:\/\/doi.org\/10.1242\/dev.202386.","DOI":"10.1242\/dev.202386"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2022.06.001"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejo\/17.4.311"},{"key":"e_1_3_3_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-36699-9"},{"key":"e_1_3_3_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13980"},{"key":"e_1_3_3_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002356"},{"key":"e_1_3_3_30_1","doi-asserted-by":"crossref","unstructured":"Shoji-Matsunaga A Ono T Hayashi M Takayanagi H Moriyama K Nakashima T. 2017. Osteocyte regulation of orthodontic force-mediated tooth movement via RANKL expression. Sci Rep. 7(1):8753. https:\/\/doi.org\/10.1038\/s41598-017-09326-7.","DOI":"10.1038\/s41598-017-09326-7"},{"key":"e_1_3_3_31_1","doi-asserted-by":"crossref","unstructured":"Siddiqui YD Nie X Wang S Abbasi Y Park L Fan X Thumbigere-Math V Chung MK. 2023. Substance P aggravates ligature-induced periodontitis in mice. Front Immunol. 14:1099017. https:\/\/doi.org\/10.3389\/fimmu.2023.1099017.","DOI":"10.3389\/fimmu.2023.1099017"},{"key":"e_1_3_3_32_1","doi-asserted-by":"crossref","unstructured":"Sun S Diggins NH Gunderson ZJ Fehrenbacher JC White FA Kacena MA. 2020. No pain no gain? The effects of pain-promoting neuropeptides and neurotrophins on fracture healing. Bone. 131:115109. https:\/\/doi.org\/10.1016\/j.bone.2019.115109.","DOI":"10.1016\/j.bone.2019.115109"},{"key":"e_1_3_3_33_1","doi-asserted-by":"crossref","unstructured":"Tsukasaki M Komatsu N Nagashima K Nitta T Pluemsakunthai W Shukunami C Iwakura Y Nakashima T Okamoto K Takayanagi H. 2018. Host defense against oral microbiota by bone-damaging T cells. Nat Commun. 9(1):701. https:\/\/doi.org\/10.1038\/s41467-018-03147-6.","DOI":"10.1038\/s41467-018-03147-6"},{"key":"e_1_3_3_34_1","doi-asserted-by":"crossref","unstructured":"Wang S Chung MK. 2020. Orthodontic force induces nerve injury-like transcriptomic changes driven by TRPV1-expressing afferents in mouse trigeminal ganglia. Mol Pain. 16:1744806920973141. https:\/\/doi.org\/10.1177\/1744806920973141.","DOI":"10.1177\/1744806920973141"},{"key":"e_1_3_3_35_1","doi-asserted-by":"crossref","unstructured":"Wang S Kim M Ali Z Ong K Pae EK Chung MK. 2019. TRPV1 and TRPV1-expressing nociceptors mediate orofacial pain behaviors in a mouse model of orthodontic tooth movement. Front Physiol. 10:1207. https:\/\/doi.org\/10.3389\/fphys.2019.01207.","DOI":"10.3389\/fphys.2019.01207"},{"key":"e_1_3_3_36_1","doi-asserted-by":"crossref","unstructured":"Wang S Ko CC Chung MK. 2024. Nociceptor mechanisms underlying pain and bone remodeling via orthodontic forces: toward no pain big gain. Front Pain Res (Lausanne). 5:1365194. https:\/\/doi.org\/10.3389\/fpain.2024.1365194.","DOI":"10.3389\/fpain.2024.1365194"},{"key":"e_1_3_3_37_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345211069956"},{"key":"e_1_3_3_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.778290"},{"key":"e_1_3_3_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034517702342"},{"key":"e_1_3_3_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2015.03.031"},{"key":"e_1_3_3_41_1","doi-asserted-by":"crossref","unstructured":"Yang CY Jeon HH Alshabab A Lee YJ Chung CH Graves DT. 2018. RANKL deletion in periodontal ligament and bone lining cells blocks orthodontic tooth movement. Int J Oral Sci. 10(1):3. https:\/\/doi.org\/10.1038\/s41368-017-0004-8.","DOI":"10.1038\/s41368-017-0004-8"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345251317429","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/00220345251317429","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345251317429","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:09:13Z","timestamp":1777496953000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/00220345251317429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1177\/00220345251317429"],"URL":"https:\/\/doi.org\/10.1177\/00220345251317429","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,12]]}}}