{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:59:06Z","timestamp":1792155546389,"version":"4.4.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chronic prostatitis\/chronic pelvic pain syndrome (CP\/CPPS) remains a challenging urological condition. This study investigated the therapeutic potential of transcutaneous electrical nerve stimulation (TENS) in experimental autoimmune prostatitis (EAP) and explored its underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Prostate tissue samples from 26 benign prostatic hyperplasia (BPH) patients were collected at Shantou Central Hospital and analyzed for M1\/M2 macrophage infiltration using immunohistochemistry (IHC). In animal experiments, 24 male Sprague\u2013Dawley rats were divided into control (\n                      <jats:italic>n<\/jats:italic>\n                      = 4), EAP (\n                      <jats:italic>n<\/jats:italic>\n                      = 7), and TENS treatment groups (\n                      <jats:italic>n<\/jats:italic>\n                      = 13; EAP + 1 Hz,\n                      <jats:italic>n<\/jats:italic>\n                      = 3; EAP + 2 Hz,\n                      <jats:italic>n<\/jats:italic>\n                      = 3; EAP + 4 Hz,\n                      <jats:italic>n<\/jats:italic>\n                      = 7). EAP was induced via prostate antigen injections, and TENS (1\u20134 Hz) was applied. In cell experiments, RAW264.7 macrophages were grouped into control, LPS-stimulated, electrical stimulation (ES)-treated (0.1\u20130.5 V\/cm), and ES + pharmacological intervention (zacopride\/probenecid) groups to study repolarization mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In BPH tissues, the M1\/M2 macrophage ratio positively correlated with inflammation severity. In EAP rats, 4 Hz TENS significantly alleviated pelvic pain, reduced proinflammatory cytokine expression, and reversed histopathological damage. TENS promoted macrophage repolarization toward the M2 phenotype. ES\n                      <jats:italic>in vitro<\/jats:italic>\n                      similarly induced M1-to-M2 repolarization, which was associated with decreased inwardly rectifying K+ channel Kir2.1 (Kir2.1) and Transient receptor potential vanilloid 2 (TRPV2) expression, membrane depolarization, reduced Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx, and a shift from NF-\u03baB\/STAT1 to STAT6 signaling. Agonists of Kir2.1 TRPV2 reversed these effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TENS alleviates CP\/CPPS by promoting M1-to-M2 macrophage repolarization, representing a promising therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1683500","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T05:40:02Z","timestamp":1768196402000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["TENS alleviates CP\/CPPS-related inflammation and pain by modulating Kir2.1-dependent macrophage polarization"],"prefix":"10.3389","volume":"16","author":[{"given":"Ting","family":"Hong","sequence":"first","affiliation":[{"name":"Clinical Medical Research Center, Shantou Central Hospital","place":["Shantou, China"]},{"name":"Shantou Key Laboratory of Basic and Translational Research of Malignant Tumors","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Medical Research Center, Shantou Central Hospital","place":["Shantou, China"]},{"name":"Shantou Key Laboratory of Basic and Translational Research of Malignant Tumors","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zepai","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Urology, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanhao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biobank, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixiu","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Biobank, Shantou Central Hospital","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyun","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shantou Central Hospital","place":["Shantou, 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