{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:21:34Z","timestamp":1792092094465,"version":"4.4.0"},"reference-count":65,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,11,11]]},"abstract":"<jats:p>\n                    PIEZO channels are mechanical force sensors involved in various biological processes, including somatosensation. To date, only a few PIEZO-binding partners have been identified, including MyoD-family inhibitor proteins (MDFI and MDFIC). Here, we show that MDFIC2, a third member of the MDFI protein family with an as-yet-unknown function, is expressed in a subset of nociceptive sensory neurons. MDFIC2 modulates both PIEZO1 and PIEZO2 gating properties by slowing their kinetics and shifting mechanical sensitivity to higher forces. Interestingly,\n                    <jats:italic toggle=\"yes\">Mdfic2<\/jats:italic>\n                    is downregulated in mouse neuropathic pain models in which mechanical allodynia is a hallmark symptom. We found that intrathecal administration of adeno-associated virus vector encoding\n                    <jats:italic toggle=\"yes\">MDFIC2<\/jats:italic>\n                    cDNA reduces mechanical sensitivity and attenuates mechanical allodynia in the spared nerve injury neuropathic pain model. These findings demonstrate a mechanism for regulating mechanosensation and highlight a potential therapeutic route for treating mechanical allodynia.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2512426122","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T16:28:36Z","timestamp":1762532916000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":18,"title":["MDFIC2 is a PIEZO channel modulator that can alleviate mechanical allodynia associated with neuropathic pain"],"prefix":"10.1073","volume":"122","author":[{"given":"Abdella M.","family":"Habib","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Qatar University Health, Qatar University","place":["Doha, Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Li","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, Division of Medicine, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for General Practice Medicine, Department of Gastroenterology, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijun","family":"Ji","sequence":"additional","affiliation":[{"name":"Center for General Practice Medicine, Department of Gastroenterology, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6368-7569","authenticated-orcid":false,"given":"Nancy","family":"Osorio","sequence":"additional","affiliation":[{"name":"Aix Marseille University, INSERM 1263, Institut National de Recherche pour l\u2019Agriculture, l\u2019Alimentation et l\u2019Environnement 1260, Centre de recherche en CardioVasculaire et Nutrition","place":["Marseille 13005, France"]},{"name":"CNRS EMR7005","place":["Marseille 13005, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2641-4339","authenticated-orcid":false,"given":"Virginie","family":"Penalba","sequence":"additional","affiliation":[{"name":"Aix Marseille University, INSERM 1263, Institut National de Recherche pour l\u2019Agriculture, l\u2019Alimentation et l\u2019Environnement 1260, Centre de recherche en CardioVasculaire et Nutrition","place":["Marseille 13005, France"]},{"name":"CNRS EMR7005","place":["Marseille 13005, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9361-6258","authenticated-orcid":false,"given":"Jesus M.","family":"Torres","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, Division of Medicine, University College London","place":["London, United Kingdom"]},{"name":"Department of Biochemistry, Molecular Biology and Immunology, Faculty of Medicine, University of Granada","place":["Granada 18016, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6020-5029","authenticated-orcid":false,"given":"Samuel J.","family":"Gossage","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, Division of Medicine, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi A.","family":"Rezai","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, Division of Medicine, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy F.","family":"Geard","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University College London School of Pharmacy, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-0949","authenticated-orcid":false,"given":"Ahad A.","family":"Rahim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University College London School of Pharmacy, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8087-2567","authenticated-orcid":false,"given":"Ahmed M. 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Coste Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. 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