{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T11:36:10Z","timestamp":1765280170600,"version":"build-2065373602"},"reference-count":31,"publisher":"BMJ","issue":"8","funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY18H310006"],"award-info":[{"award-number":["LY18H310006"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Reg Anesth Pain Med"],"accepted":{"date-parts":[[2020,5,20]]},"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Persistent neuropathic pain poses a health problem, for which effective therapy or antidote is in dire need. This work aimed to investigate the pain-relieving effect of chrysin, a natural flavonoid with monoamine oxidase inhibitory activity, in an experimental model of neuropathic pain and elucidate mechanism(s).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Chronic constriction injury (CCI) was produced by loose ligation of sciatic nerve in mice. The pain-related behaviors were examined using von Frey test and Hargreaves test. The serotonin-related mechanisms were investigated by serotonin depletion with <jats:italic>p<\/jats:italic>-chlorophenylalanine (PCPA) and antagonist tests in vivo and in vitro.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Repeated treatment of CCI mice with chrysin (orally, two times per day for 2\u2009weeks) ameliorated heat hyperalgesia and mechanical allodynia in a dose-dependent fashion (3\u201330\u2009mg\/kg). The chrysin-triggered pain relief seems serotonergically dependent, since its antihyperalgesic and antiallodynic actions were abolished by chemical depletion of serotonin by PCPA, whereas potentiated by 5-hydroxytryptophan (a precursor of 5-HT). Consistently, chrysin-treated neuropathic mice showed enhanced levels of spinal monoamines especially 5-HT, with depressed monoamine oxidase activity. Moreover, chrysin-evoked pain relief was preferentially counteracted by 5-HT<jats:sub>1A<\/jats:sub> receptor antagonist WAY-100635 delivered systematically or spinally. In vitro, chrysin (0.1\u201310\u2009nM) increased the maximum effect (Emax, shown as stimulation of [<jats:sup>35<\/jats:sup>S] GTP\u03b3S binding) of 8-OH-DPAT, a 5-HT<jats:sub>1A<\/jats:sub> agonist. Beneficially, chrysin was able to correct comorbid behavioral symptoms of depression and anxiety evoked by neuropathic pain, without causing hypertensive crisis (known as \u2018cheese reaction\u2019).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These findings confirm the antihyperalgesic and antiallodynic efficacies of chrysin, with spinal 5-HT<jats:sub>1A<\/jats:sub> receptors being critically engaged.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rapm-2020-101472","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T05:32:14Z","timestamp":1592544734000},"page":"610-619","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["5-HT<sub>1A<\/sub> receptor-mediated attenuation of heat hyperalgesia and mechanical allodynia by chrysin in mice with experimental mononeuropathy"],"prefix":"10.1136","volume":"45","author":[{"given":"Jiayi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Hunan Provincial People\u2019s Hospital, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wugeng","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"2025101109474372000_45.8.610.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.11.013"},{"key":"2025101109474372000_45.8.610.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.051508.135531"},{"key":"2025101109474372000_45.8.610.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.03.013"},{"key":"2025101109474372000_45.8.610.4","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70143-5"},{"key":"2025101109474372000_45.8.610.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2010.02999.x"},{"key":"2025101109474372000_45.8.610.6","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev-pharmtox-010818-021524","article-title":"Neuropathic pain: mechanism-based therapeutics","volume":"60","author":"Bannister","year":"2020","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"2025101109474372000_45.8.610.7","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1111\/jphp.13129","article-title":"Scutellaria baicalensis Georgi. 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