{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:18:36Z","timestamp":1777598316094,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Xanthotoxin (XAT) is a natural furanocoumarin clinically used in the treatment of skin diseases such as vitiligo and psoriasis. Recent studies have also investigated its effects on anti\u2010inflammatory, anti\u2010cognitive dysfunction, and anti\u2010amnesia as a guideline for clinic application. However, little is known about its effects on pain relief. Here, we tested the analgesic effects of XAT in serious acute pain and chronic pain models. For acute pain, we used hot\u2010, capsaicin\u2010 and formalin\u2010induced paw licking. Nociceptive threshold was measured by mechanical stimuli with von Frey filaments. For chronic pain, we injected complete Freund's adjuvant (CFA) into the mice's plantar surface of the hind paw to induce inflammatory pain. Heat and mechanical hyperalgesia were evaluated by radiant heat and von Frey filament tests, respectively. To investigate the mechanisms underlying the analgesic effect of XAT, we used calcium imaging and western blot to assess transient receptor potential vanilloid 1 (TRPV1) activity and expression in isolated L4\u2010L6 dorsal root ganglion (DRG) neurons. Haematoxylin and eosin (HE) staining, reverse transcription\u2010quantitative polymerase chain reaction (RT\u2010qPCR) and enzyme\u2010linked immunosorbent assay (ELISA) were used to examine immune cell recruitment and proinflammatory factor release from skin tissue from paw injection sites.\n                    <jats:styled-content>Our results demonstrated that XAT not only reduced acute pain behaviors generated by hot, capsaicin, and formalin but also attenuated CFA\u2010induced heat and mechanical hyperalgesia.<\/jats:styled-content>\n                    The analgesic activity of XAT may be achieved by controlling peripheral inflammation, lowering immune cell infiltration at the site of inflammatory tissue, reducing inflammatory factor production, and therefore inhibiting TRPV1 channel sensitization and expression.\n                  <\/jats:p>","DOI":"10.1111\/ejn.16119","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T05:49:11Z","timestamp":1693979351000},"page":"3605-3617","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mechanisms involved in the antinociceptive and anti\u2010inflammatory effects of xanthotoxin"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9760-2531","authenticated-orcid":false,"given":"Chan","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing Jiangsu China"},{"name":"Key Laboratory of Chinese Medicine for Prevention and Treatment of Neurological Diseases Nanjing University of Chinese Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing Jiangsu China"},{"name":"Key Laboratory of Chinese Medicine for Prevention and Treatment of Neurological Diseases Nanjing University of Chinese Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yizhi","family":"Song","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing Jiangsu China"},{"name":"Key Laboratory of Chinese Medicine for Prevention and Treatment of Neurological Diseases Nanjing University of Chinese Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing Jiangsu China"},{"name":"Key Laboratory of Chinese Medicine for Prevention and Treatment of Neurological Diseases Nanjing University of Chinese Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7918-0160","authenticated-orcid":false,"given":"Guang","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing Jiangsu China"},{"name":"Key Laboratory of Chinese Medicine for Prevention and Treatment of Neurological Diseases Nanjing University of Chinese Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juanjuan","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongxiang","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Medicine &amp; Holistic Integrative Medicine Nanjing University of Chinese Medicine  Nanjing Jiangsu China"},{"name":"Key Laboratory of Chinese Medicine for Prevention and Treatment of Neurological Diseases Nanjing University of Chinese Medicine  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2020.108997"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/md11125100"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2662"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0147-2"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.36076\/ppj.2008\/11\/S105"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(98)00064-4"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph5020114"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5464.306"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD008872.pub2"},{"issue":"6","key":"e_1_2_10_11_1","first-page":"402","article-title":"Ammoidin (xanthotoxin) in the treatment of vitiligo","volume":"81","author":"Couperus M.","year":"1954","journal-title":"California Medicine"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-016-3496-8"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/334698a0"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1501372112"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90026-7"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2019.04.033"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.02.053"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2017.05.021"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705924104"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14044"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5403-05.2006"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2015.01.011"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2016.02.019"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03514.x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001939"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2013.03.014"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0405223"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2017.09.040"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00011"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5806321"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(92)90003-T"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2006.04.001"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701148"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/AIA.0b013e318034194e"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-019-01011-3"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.16119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T13:50:05Z","timestamp":1696600205000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejn.16119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,6]]},"references-count":34,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1111\/ejn.16119"],"URL":"https:\/\/doi.org\/10.1111\/ejn.16119","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/EJN.16119\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v4\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v4\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v4\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16119\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,6]]},"assertion":[{"value":"2022-05-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}