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Adv."],"published-print":{"date-parts":[[2026,9,25]]},"abstract":"<jats:p>\n                    Pain often accompanies tissue injury and inflammation. However, in certain inflammatory contexts like periodontitis, nociceptive signaling is paradoxically suppressed. The mechanisms underlying this analgesic state remain poorly understood. Here, we investigated whether and how\n                    <jats:italic toggle=\"yes\">Porphyromonas gingivalis<\/jats:italic>\n                    (Pg) interacts with sensory neurons to induce analgesia in models of inflammatory pain. Exposure to live Pg reversed inflammatory thermal and mechanical hypersensitivity without altering local inflammation or nerve innervation. This effect required direct physical contact mediated in part by an integrin \u03b1\n                    <jats:sub>5<\/jats:sub>\n                    -FimA interface and gingipain protease activity and was not reproduced by heat-killed bacteria, protease-deficient mutants, or Pg-derived extracellular vesicles. At the neuronal level, Pg contact induced membrane hyperpolarization, reduced excitability of sensory neurons, and suppressed release of the nociceptive neuropeptide calcitonin gene-related peptide (CGRP). Proteomic and functional analyses identified downregulation of Fxyd2, a regulatory subunit of the Na\n                    <jats:sup>+<\/jats:sup>\n                    \/K\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase, linking altered ionic homeostasis to nociceptor silencing. These findings define a contact-dependent mechanism that actively suppresses peripheral pain signaling during inflammation.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee8088","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:58:53Z","timestamp":1790359133000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Direct cellular contact by\n                    <i>Porphyromonas gingivalis<\/i>\n                    suppresses nociceptor excitability and induces analgesia during inflammation"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2917-3039","authenticated-orcid":true,"given":"Sena","family":"Chung","sequence":"first","affiliation":[{"name":"Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University; Seoul, 08826, Republic of Korea."},{"name":"Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University; Seoul, 03080, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9652-7602","authenticated-orcid":true,"given":"Doyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University; Seoul, 03080, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8801-660X","authenticated-orcid":true,"given":"Byeonggeon","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University; Seoul, 03080, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4439-2547","authenticated-orcid":true,"given":"Yeon Kyeong","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University; Seoul, 03080, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0468-4433","authenticated-orcid":true,"given":"Kihwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University; Seoul, 03080, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6672-1375","authenticated-orcid":true,"given":"Hayun","family":"Kim","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Neuroscience, College of Natural Sciences, Seoul National University; Seoul, 08826, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2243-9396","authenticated-orcid":true,"given":"Hyun Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University; Seoul, 03080, Republic of Korea."},{"name":"Department of Immunology and Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University; Seoul, 03080, Republic of Korea."},{"name":"Department of Microbiology, ADA Forsyth Institute; Somerville, MA 02143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5932-9597","authenticated-orcid":true,"given":"Manda","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, ADA Forsyth Institute; Somerville, MA 02143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6228-880X","authenticated-orcid":true,"given":"Ozge","family":"Erdogan","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry and Biomaterial Sciences, Harvard School of Dental Medicine; Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Staurengo-Ferrari","sequence":"additional","affiliation":[{"name":"Department of Immunology, Blavatnik Institute, Harvard Medical School; Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0723-4841","authenticated-orcid":true,"given":"Isaac M.","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Blavatnik Institute, Harvard Medical School; Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8129-0537","authenticated-orcid":true,"given":"Mary E.","family":"Davey","sequence":"additional","affiliation":[{"name":"Department of Microbiology, ADA Forsyth Institute; Somerville, MA 02143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6496-5560","authenticated-orcid":true,"given":"Youngnim","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University; Seoul, 03080, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7975-6895","authenticated-orcid":true,"given":"Seog Bae","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University; Seoul, 03080, Republic of Korea."},{"name":"Interdisciplinary Program in Neuroscience, College of Natural Sciences, Seoul National University; Seoul, 08826, Republic of Korea."},{"name":"Department of Microbiology, ADA Forsyth Institute; Somerville, MA 02143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.07.016"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.028"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf8924"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.09.030"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2008.12.017"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01845-w"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.040"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins9070227"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00973-8"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5472.1765"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0089-x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.38"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.14219\/jada.archive.1999.0205"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.04.006"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2873"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2012.02579.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0129-6"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14899"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3785"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2014.1000764"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12479"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05753-x"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/mbo3.221"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034511400225"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2018.04.004"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00783-2"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.02.041"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.09.048"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05566.x"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2007.00779.x"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00214-2"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0363-20.2022"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.09.024"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2322574121"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.10.007"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-13-5"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-11-04880.1993"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2008.05.015"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.12"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0931278100"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1011751"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.161246"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep36407"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050658"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-12173-1"},{"key":"e_1_3_2_47_2","first-page":"100249","article-title":"An outer membrane vesicle specific lipoprotein promotes Porphyromonas gingivalis aggregation on red blood cells","volume":"7","author":"Rothenberger C. M.","year":"2024","unstructured":"C. M. Rothenberger, M. Yu, H. M. Kim, Y. W. Cheung, Y. W. Chang, M. E. Davey, An outer membrane vesicle specific lipoprotein promotes Porphyromonas gingivalis aggregation on red blood cells. Curr. Res. Microb. Sci. 7, 100249 (2024).","journal-title":"Curr. Res. Microb. Sci."},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aal2171"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-328084"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12157"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53149-7"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1177\/0192623319855969"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002542"},{"key":"e_1_3_2_54_2","first-page":"2944","article-title":"Identification of Potential Drug Targets for Antiplatelet Therapy Specifically Targeting Platelets of Old Individuals through Proteomic Analysis","volume":"11","author":"Lee S. H.","year":"2023","unstructured":"S. H. Lee, S. Cho, J. Y. Lee, J. Y. Hong, S. Kim, M. H. Jeong, W. H. Kim, Identification of Potential Drug Targets for Antiplatelet Therapy Specifically Targeting Platelets of Old Individuals through Proteomic Analysis. 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