{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:22:24Z","timestamp":1780917744332,"version":"3.54.1"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"name":"Jinlin Provincal Department of Health funds in China","award":["2019Q035"],"award-info":[{"award-number":["2019Q035"]}]},{"name":"Jinlin Provincal Department of Health funds in China","award":["2019Q018"],"award-info":[{"award-number":["2019Q018"]}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1016\/j.ejphar.2020.173322","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T14:24:19Z","timestamp":1593527059000},"page":"173322","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["Role of H2S in pain: Growing evidences of mystification"],"prefix":"10.1016","volume":"883","author":[{"given":"Jie","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaofeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2020.173322_bib1","doi-asserted-by":"crossref","DOI":"10.3390\/antiox9010031","article-title":"The inhibitory effects of slow-releasing hydrogen sulfide donors in the mechanical allodynia, grip strength deficits, and depressive-like behaviors associated with chronic osteoarthritis pain","volume":"9","author":"Batall\u00e9","year":"2019","journal-title":"Antioxidants"},{"key":"10.1016\/j.ejphar.2020.173322_bib2","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1089\/ars.2009.2927","article-title":"Hydrogen sulfide and substance P in inflammation","volume":"12","author":"Bhatia","year":"2010","journal-title":"Antioxidants Redox Signal."},{"key":"10.1016\/j.ejphar.2020.173322_bib3","article-title":"Hydrogen sulfide biosynthesis is impaired in the osteoarthritic joint","author":"Burguera","year":"2019","journal-title":"Int. J. Biometeorol."},{"key":"10.1016\/j.ejphar.2020.173322_bib4","doi-asserted-by":"crossref","first-page":"105746","DOI":"10.1016\/j.intimp.2019.105746","article-title":"Nrf2\/HO-1 signaling pathway participated in the protection of hydrogen sulfide on neuropathic pain in rats","volume":"75","author":"Chen","year":"2019","journal-title":"Int. Immunopharm."},{"key":"10.1016\/j.ejphar.2020.173322_bib5","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ejphar.2008.05.048","article-title":"Dual role of hydrogen sulfide in mechanical inflammatory hypernociception","volume":"590","author":"Cunha","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2020.173322_bib6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuropharm.2017.04.029","article-title":"Effects of natural and synthetic isothiocyanate-based H2S-releasers against chemotherapy-induced neuropathic pain: role of Kv7 potassium channels","volume":"121","author":"Di Cesare Mannelli","year":"2017","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.ejphar.2020.173322_bib7","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejphar.2014.05.023","article-title":"Role of hydrogen sulfide in the formalin-induced orofacial pain in rats","volume":"738","author":"Donatti","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2020.173322_bib8","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1111\/j.1476-5381.2010.00640.x","article-title":"Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat","volume":"159","author":"Ekundi-Valentim","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2020.173322_bib9","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.1113\/JP270963","article-title":"Regulation of the T-type Ca(2+) channel Cav3.2 by hydrogen sulfide: emerging controversies concerning the role of H2 S in nociception","volume":"594","author":"Elies","year":"2016","journal-title":"J. Physiol. (Lond.)"},{"key":"10.1016\/j.ejphar.2020.173322_bib10","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1744-8069-9-4","article-title":"Hydrogen sulfide increases excitability through suppression of sustained potassium channel currents of rat trigeminal ganglion neurons","volume":"9","author":"Feng","year":"2013","journal-title":"Mol. Pain"},{"key":"10.1016\/j.ejphar.2020.173322_bib11","doi-asserted-by":"crossref","DOI":"10.1002\/prp2.133","article-title":"NOSH-aspirin (NBS-1120), a dual nitric oxide and hydrogen sulfide-releasing hybrid, reduces inflammatory pain","volume":"3","author":"Fonseca","year":"2015","journal-title":"Pharmacol Res Perspect"},{"key":"10.1016\/j.ejphar.2020.173322_bib12","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1159\/000449449","article-title":"Hydrogen sulfide and T-type Ca2+ channels in pain processing, neuronal differentiation and neuroendocrine secretion","volume":"99","author":"Fukami","year":"2017","journal-title":"Pharmacology"},{"key":"10.1016\/j.ejphar.2020.173322_bib13","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.niox.2019.10.001","article-title":"Propargylglycine decreases neuro-immune interaction inducing pain response in temporomandibular joint inflammation model","volume":"93","author":"Garattini","year":"2019","journal-title":"Nitric Oxide"},{"key":"10.1016\/j.ejphar.2020.173322_bib14","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.neuroscience.2015.07.036","article-title":"Mechanisms of hydrogen sulfide (H2S) action on synaptic transmission at the mouse neuromuscular junction","volume":"303","author":"Gerasimova","year":"2015","journal-title":"Neuroscience"},{"key":"10.1016\/j.ejphar.2020.173322_bib15","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1007\/s11064-016-1842-z","article-title":"Endogenous CBS-H2S pathway contributes to the development of CCI-induced neuropathic pain","volume":"41","author":"Gui","year":"2016","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.ejphar.2020.173322_bib16","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.bcp.2018.01.042","article-title":"The dichotomous role of H2S in cancer cell biology? D\u00e9j\u00e0 vu all over again","volume":"149","author":"Kashfi","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejphar.2020.173322_bib17","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.pain.2007.01.026","article-title":"Hydrogen sulfide as a novel nociceptive messenger","volume":"132","author":"Kawabata","year":"2007","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2020.173322_bib18","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/978-3-319-18144-8_9","article-title":"Hydrogen sulfide and neuroinflammation","volume":"230","author":"Kida","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"key":"10.1016\/j.ejphar.2020.173322_bib19","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.niox.2014.11.014","article-title":"Inhaled hydrogen sulfide prevents neuropathic pain after peripheral nerve injury in mice","volume":"46","author":"Kida","year":"2015","journal-title":"Nitric Oxide"},{"key":"10.1016\/j.ejphar.2020.173322_bib20","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3389\/fncel.2017.00226","article-title":"Receptor mechanisms mediating the pro-nociceptive action of hydrogen sulfide in rat trigeminal neurons and meningeal afferents","volume":"11","author":"Koroleva","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.ejphar.2020.173322_bib21","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.neuroscience.2007.11.052","article-title":"A nociceptive-intensity-dependent role for hydrogen sulphide in the formalin model of persistent inflammatory pain","volume":"152","author":"Lee","year":"2008","journal-title":"Neuroscience"},{"key":"10.1016\/j.ejphar.2020.173322_bib22","doi-asserted-by":"crossref","first-page":"514898","DOI":"10.1155\/2014\/514898","article-title":"Sodium hydrosulfide relieves neuropathic pain in chronic constriction injured rats","author":"Lin","year":"2014","journal-title":"Evid Based Complement Alternat Med"},{"key":"10.1016\/j.ejphar.2020.173322_bib23","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.2147\/JPR.S161882","article-title":"Efficacy of isothiocyanate-based compounds on different forms of persistent pain","volume":"11","author":"Lucarini","year":"2018","journal-title":"J. Pain Res."},{"key":"10.1016\/j.ejphar.2020.173322_bib24","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1002\/ptr.6159","article-title":"Effect of glucoraphanin and sulforaphane against chemotherapy-induced neuropathic pain: Kv7 potassium channels modulation by H2 S release in vivo","volume":"32","author":"Lucarini","year":"2018","journal-title":"Phytother Res."},{"key":"10.1016\/j.ejphar.2020.173322_bib25","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.pain.2008.12.021","article-title":"Hyperalgesia induced by spinal and peripheral hydrogen sulfide: evidence for involvement of Cav3.2 T-type calcium channels","volume":"142","author":"Maeda","year":"2009","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2020.173322_bib26","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40635-020-0296-4","article-title":"Emerging pharmacological tools to control hydrogen sulfide signaling in critical illness","volume":"8","author":"Marutani","year":"2020","journal-title":"Intens. Care Med Exp"},{"key":"10.1016\/j.ejphar.2020.173322_bib27","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.jphs.2019.07.010","article-title":"Genetic deletion of Cav3.2 T-type calcium channels abolishes H2S-dependent somatic and visceral pain signaling in C57BL\/6 mice","volume":"140","author":"Matsui","year":"2019","journal-title":"J. Pharmacol. Sci."},{"key":"10.1016\/j.ejphar.2020.173322_bib28","doi-asserted-by":"crossref","first-page":"172404","DOI":"10.1016\/j.ejphar.2019.172404","article-title":"4-Methylbenzenecarbothioamide, a hydrogen sulfide donor, inhibits tumor necrosis factor-\u03b1 and CXCL1 production and exhibits activity in models of pain and inflammation","volume":"856","author":"Melo","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2020.173322_bib29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1744-8069-10-9","article-title":"Upregulation of cystathionine-\u03b2-synthetase expression contributes to inflammatory pain in rat temporomandibular joint","volume":"10","author":"Miao","year":"2014","journal-title":"Mol. Pain"},{"key":"10.1016\/j.ejphar.2020.173322_bib30","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/978-3-319-18144-8_10","article-title":"Brain, learning, and memory: role of H2S in neurodegenerative diseases","volume":"230","author":"Nagpure","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"key":"10.1016\/j.ejphar.2020.173322_bib31","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1111\/j.1476-5381.2012.01886.x","article-title":"Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice","volume":"166","author":"Okubo","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2020.173322_bib32","doi-asserted-by":"crossref","first-page":"9049782","DOI":"10.1155\/2016\/9049782","article-title":"Physiological importance of hydrogen sulfide: emerging potent neuroprotector and neuromodulator","author":"Panthi","year":"2016","journal-title":"Oxid Med Cell Longev"},{"key":"10.1016\/j.ejphar.2020.173322_bib33","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.niox.2017.01.012","article-title":"Analgesic effect of dimethyl trisulfide in mice is mediated by TRPA1 and sst4 receptors","volume":"65","author":"Pozsgai","year":"2017","journal-title":"Nitric Oxide"},{"key":"10.1016\/j.ejphar.2020.173322_bib34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12868-018-0483-3","article-title":"Possible involvement of peripheral TRP channels in the hydrogen sulfide-induced hyperalgesia in diabetic rats","volume":"20","author":"Roa-Coria","year":"2019","journal-title":"BMC Neurosci."},{"key":"10.1016\/j.ejphar.2020.173322_bib35","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2174\/187152811794776295","article-title":"The neurophysiology of hydrogen sulfide","volume":"10","author":"Rong","year":"2011","journal-title":"Inflamm. Allergy - Drug Targets"},{"key":"10.1016\/j.ejphar.2020.173322_bib36","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.physbeh.2018.02.007","article-title":"The therapeutic potential of cystathionine gamma-lyase in temporomandibular inflammation-induced orofacial hypernociception","volume":"188","author":"Santos","year":"2018","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.ejphar.2020.173322_bib37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.bbrc.2014.01.185","article-title":"Endogenous and exogenous hydrogen sulfide facilitates T-type calcium channel currents in Cav3.2-expressing HEK293 cells","volume":"445","author":"Sekiguchi","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejphar.2020.173322_bib38","doi-asserted-by":"crossref","first-page":"901","DOI":"10.36076\/ppj.2009\/12\/901","article-title":"Hydrogen sulfide's involvement in modulating nociception","volume":"12","author":"Smith","year":"2009","journal-title":"Pain Physician"},{"key":"10.1016\/j.ejphar.2020.173322_bib39","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.brainres.2015.07.058","article-title":"The H2S-producing enzyme CSE is dispensable for the processing of inflammatory and neuropathic pain","volume":"1624","author":"Syhr","year":"2015","journal-title":"Brain Res."},{"key":"10.1016\/j.ejphar.2020.173322_bib40","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/jnr.23251","article-title":"Inflammatory acidic pH enhances hydrogen sulfide-induced transient receptor potential ankyrin 1 activation in RIN-14B cells","volume":"91","author":"Takahashi","year":"2013","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.ejphar.2020.173322_bib41","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.pain.2010.04.022","article-title":"Upregulation of Ca(v)3.2 T-type calcium channels targeted by endogenous hydrogen sulfide contributes to maintenance of neuropathic pain","volume":"150","author":"Takahashi","year":"2010","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2020.173322_bib42","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/978-3-319-18144-8_11","article-title":"H2S and pain: a novel aspect for processing of somatic, visceral and neuropathic pain signals","volume":"230","author":"Terada","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"key":"10.1016\/j.ejphar.2020.173322_bib43","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1254\/fpj.154.128","article-title":"[Regulation of Cav3.2-mediated pain signals by hydrogen sulfide]","volume":"154","author":"Tsubota","year":"2019","journal-title":"Nippon Yakurigaku Zasshi"},{"key":"10.1016\/j.ejphar.2020.173322_bib44","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.bbrc.2019.02.102","article-title":"Dietary ascorbic acid restriction in GNL\/SMP30-knockout mice unveils the role of ascorbic acid in regulation of somatic and visceral pain sensitivity","volume":"511","author":"Tsubota","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejphar.2020.173322_bib45","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1111\/bph.14641","article-title":"A proof-of-concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide-releasing anti-inflammatory drug","volume":"177","author":"Wallace","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2020.173322_bib46","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1089\/ars.2017.7068","article-title":"Hydrogen sulfide-releasing therapeutics: translation to the clinic","volume":"28","author":"Wallace","year":"2018","journal-title":"Antioxidants Redox Signal."},{"key":"10.1016\/j.ejphar.2020.173322_bib47","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12990-015-0012-7","article-title":"Sensitization of P2X3 receptors by cystathionine \u03b2-synthetase mediates persistent pain hypersensitivity in a rat model of lumbar disc herniation","volume":"11","author":"Wang","year":"2015","journal-title":"Mol. Pain"},{"key":"10.1016\/j.ejphar.2020.173322_bib48","doi-asserted-by":"crossref","first-page":"38188","DOI":"10.1038\/srep38188","article-title":"Inhibition of cystathionine \u03b2-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation","volume":"6","author":"Yan","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejphar.2020.173322_bib49","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1017\/S1461145714000583","article-title":"Hydrogen sulfide inhibits opioid withdrawal-induced pain sensitization in rats by down-regulation of spinal calcitonin gene-related peptide expression in the spine","volume":"17","author":"Yang","year":"2014","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"10.1016\/j.ejphar.2020.173322_bib50","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jns.2016.02.058","article-title":"Upregulation of spinal NMDA receptors mediates hydrogen sulfide-induced hyperalgesia","volume":"363","author":"Zhao","year":"2016","journal-title":"J. Neurol. Sci."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299920304143?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299920304143?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T22:38:22Z","timestamp":1757975902000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299920304143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":50,"alternative-id":["S0014299920304143"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2020.173322","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Role of H2S in pain: Growing evidences of mystification","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2020.173322","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"173322"}}