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To elucidate the pain relief mechanism induced by the patches, we established a quantitative method for estimating the pain reduction and investigated the brain regions that change in association with pain relief. We first attempted to quantify the pain relief using transcutaneous electric stimulation (TCES) and a visual analog scale (VAS), and then applied near-infrared spectroscopy (NIRS) to the prefrontal cortex, including the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC). We also examined the salivary oxytocin levels, which are thought to reflect oxytocin secretion levels from the posterior pituitary in the brain. Application of pyramidal thorn patches to pain regions decreased the pain degree estimated using TCES and VAS. Oxyhemoglobin levels were likely to be decreased in the left DLPFC on the basis of NIRS measurements during patch treatment, suggesting that the left DLPFC is involved in pain relief. On the other hand, the salivary oxytocin levels varied widely. A potential reason for the varying salivary oxytocin levels is its utilization in the pain region as an analgesic agent. Our results suggest that the left DLPFC will become a target brain region for pain therapy.<\/jats:p>","DOI":"10.1371\/journal.pone.0256626","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T17:48:55Z","timestamp":1629740935000},"page":"e0256626","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pain relief associated with decreased oxyhemoglobin level in left dorsolateral prefrontal cortex"],"prefix":"10.1371","volume":"16","author":[{"given":"Shun","family":"Miyashiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurika","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Nagaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rei","family":"Shima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshizumi","family":"Muta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruyuki","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuri","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Hori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Oka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusako","family":"Koshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1877-6566","authenticated-orcid":true,"given":"Etsuro","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"pone.0256626.ref001","author":"National Center for Complementary and Integrative Health, National Institutes of Health, USA.","year":"2016","journal-title":"Use of Complementary and Integrative Health Approaches in the United States, 2012"},{"key":"pone.0256626.ref002","doi-asserted-by":"crossref","first-page":"1260285","DOI":"10.1155\/2018\/1260285","article-title":"A proposed molecular mechanism for physical analgesia in chronic pain","volume":"2018","author":"N Saito","year":"2018","journal-title":"Neural Plast."},{"key":"pone.0256626.ref003","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/kjm2.12044","article-title":"Adhesive pyramidal thorn patches provide pain relief to athletes","volume":"35","author":"N Saito","year":"2019","journal-title":"Kaohsiung J Med Sci"},{"key":"pone.0256626.ref004","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.neuroscience.2021.01.001","article-title":"Cortical modulation of nociception","volume":"458","author":"M Gamal-Eltrabily","year":"2021","journal-title":"Neuroscience"},{"key":"pone.0256626.ref005","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/j.pain.2013.07.020","article-title":"Prefrontal cortex and mediodorsal thalamus reduced connectivity is associated with spatial working memory impairment in rats with inflammatory pain","volume":"154","author":"H Cardoso-Cruz","year":"2013","journal-title":"Pain"},{"key":"pone.0256626.ref006","doi-asserted-by":"crossref","first-page":"7574","DOI":"10.1523\/JNEUROSCI.0174-13.2013","article-title":"Chronic pain: lost inhibition","volume":"33","author":"LA Henderson","year":"2013","journal-title":"J Neurosci"},{"key":"pone.0256626.ref007","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1097\/j.pain.0000000000000318","article-title":"Roles of prefrontal cortex and paraventricular thalamus in affective and mechanical components of visceral nociception","volume":"156","author":"A Jurik","year":"2015","journal-title":"Pain"},{"key":"pone.0256626.ref008","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.3390\/ijms21103440","article-title":"The medial prefrontal cortex as a central hub for mental comorbidities associated with chronic pain","volume":"21","author":"KK Kummer","year":"2020","journal-title":"Int J Mol Sci"},{"key":"pone.0256626.ref009","first-page":"188","article-title":"Facilitating action of medial prefrontal cortex upon the noxious thermally-evoked responses in thalamic centralis lateralis nucleus","volume":"85","author":"M Cond\u00e9s-Lara","year":"1991","journal-title":"J Physiol. 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