{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T04:31:25Z","timestamp":1782880285661,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japanese Society for the Promotion of Science","award":["22K10232"],"award-info":[{"award-number":["22K10232"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>While gut microbiota-derived short-chain fatty acids (SCFAs) are recognized to modulate pathological pain by decreasing inflammation, the neurophysiological basis for SCFAs, butyrate\u2019s ability to reduce hyperexcitability in nociceptive primary neurons during inflammatory conditions is still unknown. The objective of this study was to determine, using in vivo conditions, whether systemic butyrate administration attenuates inflammation-induced hyperexcitability of trigeminal ganglion (TG) primary neurons and the concomitant mechanical inflammatory hyperalgesia. Rats received complete Freund\u2019s adjuvant (CFA) injections in their whisker pads to induce inflammation. CFA-inflamed rats showed a significantly lower mechanical stimulation-induced escape threshold compared to na\u00efve rats. Systemic butyrate administration restored the mechanical threshold to levels comparable to na\u00efve rats within four days. Four days of butyrate administration significantly decreased the mean increased discharge frequency of TG neurons to both non-noxious and noxious mechanical stimuli in inflamed rats. The increased mean spontaneous discharge of TG neurons in inflamed rats significantly decreased four days after butyrate administration. Collectively, our findings indicate that butyrate reduces inflammatory hyperexcitability in nociceptive primary TG neurons, thereby alleviating inflammatory hyperalgesia. These results suggest that butyrate may serve as a promising therapeutic approach for the prevention of trigeminal inflammatory mechanical hyperalgesia and its clinical manifestations.<\/jats:p>","DOI":"10.3390\/molecules30112407","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T08:34:13Z","timestamp":1748853253000},"page":"2407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Short-Chain Fatty Acid, Butyrate, Suppresses the Hyperexcitability of Rat Nociceptive Primary Neurons Involved in Inflammatory Hyperalgesia"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0843-2608","authenticated-orcid":false,"given":"Yukito","family":"Sashide","sequence":"first","affiliation":[{"name":"Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara 252-5201, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syogo","family":"Utugi","sequence":"additional","affiliation":[{"name":"Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara 252-5201, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6890-0943","authenticated-orcid":false,"given":"Mamoru","family":"Takeda","sequence":"additional","affiliation":[{"name":"Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara 252-5201, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sessle, B.J. 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