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This study evaluates the preemptive analgesic effects and their duration of low\u2010 (LT: 4\u2009Hz) and high\u2010frequency TENS (HT: 100\u2009Hz) using a rat model of acute inflammatory pain. Acute inflammation was induced by injecting 1% formalin into the hind paws of rats. LT or HT was applied for 30\u2009min before formalin injection. Pain\u2010related behaviors, such as licking, flinching, and lifting, were recorded for 60\u2009min postinjection. Immunohistochemistry was used to assess the number of phosphorylated extracellular signal\u2010regulated kinase (pERK)\u2010 and c\u2010fos\u2010positive cells in the spinal cord. Naloxone, a \u03bc\u2010opioid receptors (MORs) antagonist, and naltrindole, a \u03b4\u2010opioid receptors (DORs) antagonist, were administered before TENS application. Pain behavior duration and pERK\u2010 and c\u2010fos\u2010positive cell expression were then measured. LT and HT pretreatment significantly reduced both pain behaviors and the number of pERK\u2010 and c\u2010fos\u2010positive cells postformalin injection. Naloxone and naltrindole partially reversed the effects of LT and HT, respectively. Notably, HT's analgesic effect lasted up to 120\u2009min whereas that of LT persisted for 90\u2009min. LT and HT effectively exerted their preemptive analgesic effects on acute inflammatory pain by inhibiting pERK and c\u2010fos expression in the spinal cord. HT presented a longer\u2010lasting effect compared to LT. MOR and DOR activation may contribute to LT and HT's analgesic mechanisms, respectively.<\/jats:p>","DOI":"10.1002\/kjm2.12818","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T16:53:41Z","timestamp":1709744021000},"page":"456-466","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Duration of the preemptive analgesic effects of low\u2010 and high\u2010frequency transcutaneous electrical nerve stimulation in rats with acute inflammatory pain"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7912-8984","authenticated-orcid":false,"given":"Hideshi","family":"Ikemoto","sequence":"first","affiliation":[{"name":"Department of Physiology Showa University Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of 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