{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:16:21Z","timestamp":1787015781582,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T00:00:00Z","timestamp":1655510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","award":["ncRNAPain 602133"],"award-info":[{"award-number":["ncRNAPain 602133"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009379","name":"Interdisziplin\u00e4res Zentrum f\u00fcr Klinische Forschung, Universit\u00e4tsklinikum W\u00fcrzburg","doi-asserted-by":"publisher","award":["Z\u20102\/61"],"award-info":[{"award-number":["Z\u20102\/61"]}],"id":[{"id":"10.13039\/501100009379","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KFO 5001"],"award-info":[{"award-number":["KFO 5001"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["nyaspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired\u2014partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA\u201021\u20105p (miR\u201021) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features. However, little is known about other functions. Here, we characterized miR\u201021 in neuropathic pain and its impact on the BNB in a human\u2010murine back translational approach. MiR\u201021 expression was elevated in plasma of patients with CRPS as well as in nerves of mice after transient and persistent nerve injury. Mice presented with BNB leakage, as well as loss of claudin\u20101 in both injured and spared nerves. Moreover, the putative miR\u201021 target RECK was decreased and downstream\n                    <jats:italic>Mmp9<\/jats:italic>\n                    upregulated, as was\n                    <jats:italic>Tgfb<\/jats:italic>\n                    .\n                    <jats:italic>In vitro<\/jats:italic>\n                    experiments in human epithelial cells confirmed a downregulation of\n                    <jats:italic>CLDN1<\/jats:italic>\n                    by miR\u201021 mimics via inhibition of the\n                    <jats:italic>RECK\/MMP9<\/jats:italic>\n                    pathway but not\n                    <jats:italic>TGFB<\/jats:italic>\n                    . Perineurial miR\u201021 mimic application in mice elicited mechanical hypersensitivity, while local inhibition of miR\u201021 after nerve injury reversed it. In summary, the data support a novel role for miR\u201021, independent of prior inflammation, in elicitation of pain and impairment of the BNB via RECK\/MMP9.\n                  <\/jats:p>","DOI":"10.1111\/nyas.14816","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T06:32:56Z","timestamp":1655533976000},"page":"184-195","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["MicroRNA\u201021\u20105p functions via RECK\/MMP9 as a proalgesic regulator of the blood nerve barrier in nerve injury"],"prefix":"10.1111","volume":"1515","author":[{"given":"Ann Kristin","family":"Reinhold","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine University Hospital W\u00fcrzburg, Center for Interdisciplinary Pain Medicine  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1293-2484","authenticated-orcid":false,"given":"Susanne M.","family":"Krug","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology\/Nutritional Medicine Charit\u00e9 \u2010 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellaine","family":"Salvador","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine University Hospital W\u00fcrzburg, Center for Interdisciplinary Pain Medicine  W\u00fcrzburg Germany"},{"name":"Section Experimental Neurosurgery, Department of Neurosurgery University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reine S.","family":"Sauer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine University Hospital W\u00fcrzburg, Center for Interdisciplinary Pain Medicine  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Karl\u2010Sch\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Malcangio","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Sommer","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2018.20"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-016-1920-8"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00936"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2014.04.029"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-9-195"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/NS20190099"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2017.07.041"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.04.089"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01841-5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113915"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.03.032"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066814"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.306092"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1723"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120800109"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24046"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2007.01631.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001617"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90209-6"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(00)00276-1"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1965.10480843"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.11.053"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2579"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00020.2014"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.1998.11740483"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.563166"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21257"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00019"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-02125-4"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.131599"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2020.1777767"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.07.015"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2018.5728"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kjms.2018.05.006"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.2147\/JAA.S307165"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.22.13221"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5949.2012.00344.x"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01519"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz885"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2021.04.002"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2019.01.008"},{"key":"e_1_2_7_43_1","article-title":"Microvascular 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