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The mechanically activated ion channel Piezo2 plays a role in mechanical sensitization; however, there has been little progress in examining therapeutics that target Piezo2. The goal of this study was to assess the effectiveness of FM\u2010dye in reducing acute inflammatory and osteoarthritic (OA) knee pain in mice through Piezo2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Wild\u2010type or nociceptor\u2010specific Piezo2 conditional knockout (Piezo2cko) mice were used. The complete Freund's adjuvant (CFA) model of acute inflammatory knee pain, the partial medial meniscectomy (PMX) OA model, and ageing\u2010associated OA mouse models were used. Pain\u2010related behaviours (knee hyperalgesia, weight bearing asymmetry) were established prior to intra\u2010articular injection of FM\u2010dye (5\u00a0nmol in 2.5\u00a0\u03bcl) or vehicle. In vivo calcium imaging of the L4 dorsal root ganglion (DRG) was performed using Na\n                      <jats:sub>V<\/jats:sub>\n                      1.8\u2010GCaMP6 mice in the CFA model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>In the CFA model, female and male mice intra\u2010articularly injected with FM1\u201043 exhibited reduced knee hyperalgesia 90\u2009min post\u2010injection. In vivo calcium imaging of the DRG demonstrated a reduction in nociceptor responses to mechanical force applied to the knee of CFA mice following FM\u2010dye. Following PMX, intra\u2010articular injection of FM1\u201043 reduced knee hyperalgesia in wild\u2010type mice but not in Piezo2cko mice; weight bearing asymmetry was also reduced. In mice with age\u2010associated OA, intra\u2010articular injection of FM\u2010dyes reduced knee hyperalgesia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Inhibiting Piezo2 pharmacologically reduced pain\u2010related behaviours in mouse models of inflammatory and OA knee pain, providing evidence of the therapeutic potential of targeting Piezo2.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70306","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T01:54:51Z","timestamp":1767664491000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["FM\u2010dye inhibition of Piezo2 relieves mechanically evoked pain in mouse models of acute inflammatory and osteoarthritic knee pain"],"prefix":"10.1111","author":[{"given":"Natalie S.","family":"Adamczyk","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology Rush University Medical Center  Chicago Illinois USA"},{"name":"Chicago Center on Musculoskeletal Pain  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology Rush University Medical Center  Chicago Illinois USA"},{"name":"Chicago Center on Musculoskeletal Pain  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alia M.","family":"Obeidat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology Rush University Medical Center  Chicago Illinois USA"},{"name":"Chicago Center on Musculoskeletal Pain  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology Rush University Medical Center  Chicago Illinois USA"},{"name":"Chicago Center on Musculoskeletal Pain  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian T.","family":"David","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjun","family":"Ren","sequence":"additional","affiliation":[{"name":"Chicago Center on Musculoskeletal Pain  Chicago Illinois USA"},{"name":"Department of Pharmacology Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Miller","sequence":"additional","affiliation":[{"name":"Chicago Center on Musculoskeletal Pain  Chicago Illinois USA"},{"name":"Department of Pharmacology Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Marie","family":"Malfait","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology Rush University Medical Center  Chicago Illinois USA"},{"name":"Chicago Center on Musculoskeletal Pain  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology Rush University Medical Center  Chicago Illinois USA"},{"name":"Chicago Center on Musculoskeletal Pain  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2017.1279370"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16178"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.07.022"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-2720.2004.01348.x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.09.014"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32340-0"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3388-05.2006"},{"key":"e_1_2_12_10_1","article-title":"FM1\u201043 is a permeant blocker of mechanosensitive ion channels in sensory neurons and inhibits behavioural responses to mechanical stimuli","volume":"3","author":"Drew L. 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