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Considering the unsatisfactory results of current therapeutic management for chronic pain conditions, we aimed to review saffron's analgesic activity and underlying mechanisms. Saffron showed antinociceptive activities in formalin\u2010, carrageenan\u2010, and capsaicin\u2010induced experimental pain models. Saffron analgesic activities affected several targets, including ion channels of nociceptors; the adrenergic system and central histaminic system; inhibition of inflammatory pathways, apoptotic pathways, and oxidative stress; regulation of NO pathway, and the endocannabinoid system. Clinical studies showed analgesia of Saffron in rheumatoid arthritis, after\u2010pain following childbirth, dysmenorrhea, and fibromyalgia. Our literature review showed that saffron can be beneficial as an adjunct therapy to commonly used analgesics in practice, particularly in chronic pain conditions.<\/jats:p>","DOI":"10.1002\/ptr.7968","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T06:19:12Z","timestamp":1690957152000},"page":"5041-5057","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Saffron (<i>Crocus sativus<\/i>) and its constituents for pain management: A review of current evidence"],"prefix":"10.1002","volume":"37","author":[{"given":"Ali Mohammad","family":"Pourbagher\u2010Shahri","sequence":"first","affiliation":[{"name":"Neuroscience Research Center Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0023-6470","authenticated-orcid":false,"given":"Fatemeh","family":"Forouzanfar","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Department of Neuroscience, Faculty of Medicine Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,8]]},"reference":[{"issue":"2","key":"e_1_2_17_2_1","first-page":"1915","article-title":"The effect of oral capsules of saffron on anxiety and fatigue during the first stage of labor","volume":"23","author":"Ahmadi S.","year":"2015","journal-title":"Journal of Shahid Sadoughi University of Medical Sciences"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27103339"},{"issue":"2","key":"e_1_2_17_4_1","first-page":"73","article-title":"Increased miscarriage rate in female farmers working in saffron fields: A possible effect of saffron toxicity","volume":"3","author":"Ajam M.","year":"2014","journal-title":"Asia Pacific Journal of Medical Toxicology"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6882-4-12"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.1647"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1590\/0001-3765201420140067"},{"issue":"1","key":"e_1_2_17_8_1","first-page":"187","article-title":"Enhancement of antinociceptive effect by co\u2010administration of amitriptyline and Crocus sativus in a rat model of neuropathic pain","volume":"16","author":"Amin B.","year":"2017","journal-title":"Iranian Journal of Pharmaceutical Research: IJPR"},{"key":"e_1_2_17_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2012.03.022"},{"key":"e_1_2_17_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110452"},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2011.614934"},{"key":"e_1_2_17_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-009-8740-7"},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574888X15666200214112908"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.09.014"},{"key":"e_1_2_17_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5021"},{"key":"e_1_2_17_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6643950"},{"key":"e_1_2_17_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17041191"},{"key":"e_1_2_17_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.028"},{"key":"e_1_2_17_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)01313-6"},{"key":"e_1_2_17_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0972"},{"issue":"2","key":"e_1_2_17_21_1","first-page":"110","article-title":"Toxicology effects of saffron and its constituents: A review","volume":"20","author":"Bostan H. 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