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The aim of this study was to elucidate the underlying analgesic mechanism of the AT-04 using the partial sciatic nerve ligation (PSL) model as an animal model of neuropathic pain. AT-04 was applied to PSL model rats with hyperalgesia and its pain-improving effect was verified by examining mechanical allodynia using the von Frey method. The results demonstrated a significant improvement in hyperalgesia in PSL model rats. We also examined the involvement of descending pain modulatory systems in the analgesic effects of AT-04 using antagonism by serotonin and noradrenergic receptor antagonists. These antagonists significantly reduced the analgesic effect of AT-04 on pain in PSL model rats by approximately 50%. We also measured the amount of serotonin and noradrenaline in the spinal fluid of PSL model rats using microdialysis during AT-04 treatment. Both monoamines were significantly increased by magnetic fields irradiation with AT-04. Furthermore, we evaluated the involvement of opioid analgesia in the analgesic effects of AT-04 using naloxone, the main antagonist of the opioid receptor, and found that it significantly antagonized the effects by approximately 60%. Therefore, the analgesic effects of AT-04 in PSL model rats involve both the endogenous pain modulation systems, including the descending pain modulatory system and the opioid analgesic system.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s10571-023-01430-9","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T06:01:25Z","timestamp":1699336885000},"page":"4345-4362","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Neuromodulation Through Magnetic Fields Irradiation with AT-04 Improves Hyperalgesia in a Rat Model of Neuropathic Pain via Descending Pain Modulatory Systems and Opioid Analgesia"],"prefix":"10.1007","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3898-5912","authenticated-orcid":false,"given":"Tatsuro","family":"Kohno","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1494-5267","authenticated-orcid":false,"given":"Kaori","family":"Takaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7803-473X","authenticated-orcid":false,"given":"Kaori","family":"Kishita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8283-7251","authenticated-orcid":false,"given":"Kazunori","family":"Mitsutake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1921-407X","authenticated-orcid":false,"given":"Nozomu","family":"Tofuku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7011-5131","authenticated-orcid":false,"given":"Iwao","family":"Kishita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"1430_CR1","first-page":"219","volume":"31","author":"SE Aragona","year":"2017","unstructured":"Aragona SE, Mereghetti G, Lotti J, Vosa A, Lotti T, Canavesi E (2017) Electromagnetic field in control tissue regeneration, pelvic pain, neuro-inflammation and modulation of non-neuronal cells. 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Phys Ther 102(10):pzac104.\u00a0https:\/\/doi.org\/10.1093\/ptj\/pzac104","journal-title":"Phys Ther"}],"container-title":["Cellular and Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10571-023-01430-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10571-023-01430-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10571-023-01430-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T06:13:03Z","timestamp":1700547183000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10571-023-01430-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11]]},"references-count":41,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["1430"],"URL":"https:\/\/doi.org\/10.1007\/s10571-023-01430-9","relation":{},"ISSN":["0272-4340","1573-6830"],"issn-type":[{"value":"0272-4340","type":"print"},{"value":"1573-6830","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11]]},"assertion":[{"value":"19 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Several authors (Kaori Takaki, Kaori Kishita, Kazunori Mitsutake, Nozomu Tofuku, Iwao Kishita) are employees of Peace of Mind Co., Ltd., which developed the AT-04 device and holds a patent related to its technology (patent number: JP4111995, JP4821957). Additionally, one of these authors (Iwao Kishita) are also inventors of the device. In addition, external collaborators (Tatsuro Kohno) participated in this study but do not have any affiliations or interests that could be perceived as a conflict of interest. Despite these affiliations and relationships, the authors declare that the potential conflict of interest did not influence the study design, data collection, analysis, interpretation, or manuscript preparation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}