{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:18:52Z","timestamp":1790363932931,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A2C2003750"],"award-info":[{"award-number":["NRF-2019R1A2C2003750"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A2C1005791"],"award-info":[{"award-number":["NRF-2019R1A2C1005791"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lumbar spinal stenosis (LSS) is a major cause of chronic neuropathic back and\/or leg pain. Recently, we demonstrated that a significant number of macrophages infiltrated into the cauda equina after compression injury, causing neuroinflammation, and consequently mediating neuropathic pain development and\/or maintenance. However, the molecular mechanisms underlying macrophage infiltration and activation have not been elucidated. Here, we demonstrated the critical role of histone H3K27 demethylase Jmjd3 in blood-nerve barrier dysfunction following macrophage infiltration and activation in LSS rats. The LSS rat model was induced by cauda equina compression using a silicone block within the epidural spaces of the L5-L6 vertebrae with neuropathic pain developing 4 weeks after compression. We found that Jmjd3 was induced in the blood vessels and infiltrated macrophages in a rat model of neuropathic pain. The blood-nerve barrier permeability in the cauda equina was increased after compression and significantly attenuated by the Jmjd3 demethylase inhibitor, GSK-J4. GSK-J4 also inhibited the expression and activation of MMP-2 and MMP-9 and significantly alleviated the loss of tight junction proteins and macrophage infiltration. Furthermore, the activation of a macrophage cell line, RAW 264.7, by LPS was significantly alleviated by GSK-J4. Finally, GSK-J4 and a potential Jmjd3 inhibitor, gallic acid, significantly inhibited mechanical allodynia in LSS rats. Thus, our findings suggest that Jmjd3 mediates neuropathic pain development and maintenance by inducing macrophage infiltration and activation after cauda equina compression and thus may serve as a potential therapeutic target for LSS-induced neuropathic pain.<\/jats:p>","DOI":"10.3390\/ijms222413426","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T09:34:25Z","timestamp":1639474465000},"page":"13426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Jmjd3 Mediates Neuropathic Pain by Inducing Macrophage Infiltration and Activation in Lumbar Spinal Stenosis Animal Model"],"prefix":"10.3390","volume":"22","author":[{"given":"Jeeyoun","family":"Lee","sequence":"first","affiliation":[{"name":"Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haeyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chansol","family":"Park","sequence":"additional","affiliation":[{"name":"Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangryong","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeyoung","family":"Yune","sequence":"additional","affiliation":[{"name":"Age-Related and Brain Diseases Research Center, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.3892\/mmr.2013.1723","article-title":"Brain-derived neurotrophic factor expression in dorsal root ganglia of a lumbar spinal stenosis model in rats","volume":"8","author":"Li","year":"2013","journal-title":"Mol. 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