{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:33:19Z","timestamp":1790371999257,"version":"4.1.0"},"reference-count":94,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004263","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul","doi-asserted-by":"publisher","award":["21\/2551\u20100001966\u20102"],"award-info":[{"award-number":["21\/2551\u20100001966\u20102"]}],"id":[{"id":"10.13039\/501100004263","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GMR22T1070"],"award-info":[{"award-number":["GMR22T1070"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010678","name":"H2020 Food","doi-asserted-by":"publisher","award":["304985\/2020\u20101"],"award-info":[{"award-number":["304985\/2020\u20101"]}],"id":[{"id":"10.13039\/100010678","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010678","name":"H2020 Food","doi-asserted-by":"publisher","award":["150611\/2022\u20106"],"award-info":[{"award-number":["150611\/2022\u20106"]}],"id":[{"id":"10.13039\/100010678","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Fibromyalgia is a complex clinical disorder with an unknown aetiology, characterized by generalized pain and co\u2010morbid symptoms such as anxiety and depression. An imbalance of oxidants and antioxidants is proposed to play a pivotal role in the pathogenesis of fibromyalgia symptoms. However, the precise mechanisms by which oxidative stress contributes to fibromyalgia\u2010induced pain remain unclear. The transient receptor potential ankyrin 1 (TRPA1) channel, known as both a pain sensor and an oxidative stress sensor, has been implicated in various painful conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The feed\u2010forward mechanism that implicates reactive oxygen species (ROS) driven by TRPA1 was investigated in a reserpine\u2010induced fibromyalgia model in C57BL\/6J mice employing pharmacological interventions and genetic approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Reserpine\u2010treated mice developed pain\u2010like behaviours (mechanical\/cold hypersensitivity) and early anxiety\u2010depressive\u2010like disorders, accompanied by increased levels of oxidative stress markers in the sciatic nerve tissues. These effects were not observed upon pharmacological blockade or global genetic deletion of the TRPA1 channel and macrophage depletion. Furthermore, we demonstrated that selective silencing of TRPA1 in Schwann cells reduced reserpine\u2010induced neuroinflammation (NADPH oxidase 1\u2010dependent ROS generation and macrophage increase in the sciatic nerve) and attenuated fibromyalgia\u2010like behaviours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Activated Schwann cells expressing TRPA1 promote an intracellular pathway culminating in the release of ROS and recruitment of macrophages in the mouse sciatic nerve. These cellular and molecular events sustain mechanical and cold hypersensitivity in the reserpine\u2010evoked fibromyalgia model. Targeting TRPA1 channels on Schwann cells could offer a novel therapeutic approach for managing fibromyalgia\u2010related behaviours.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16413","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T23:10:11Z","timestamp":1716333011000},"page":"3445-3461","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Schwann cell TRPA1 elicits reserpine\u2010induced fibromyalgia pain in mice"],"prefix":"10.1111","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6020-8274","authenticated-orcid":false,"given":"Evelyne Silva","family":"Brum","sequence":"first","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences Federal University of Santa Maria  Santa Maria Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Fernanda Pessano","family":"Fialho","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences Federal University of Santa Maria  Santa Maria Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Souza Monteiro de Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Clinical Pharmacology Unit University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Landini","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Clinical Pharmacology Unit University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Marini","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Clinical Pharmacology Unit University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Titiz","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Clinical Pharmacology Unit University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna Luiza","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Heterocycle Chemistry Nucleus (NUQUIMHE) Federal University of Santa Maria  Santa Maria Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa Piccinin","family":"Frizzo","sequence":"additional","affiliation":[{"name":"Heterocycle Chemistry Nucleus (NUQUIMHE) Federal University of Santa Maria  Santa Maria Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Henrique Silva","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Genetic and Biochemistry University of Uberl\u00e2ndia  Uberl\u00e2ndia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela Mano","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Mattar","family":"Cunha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1ssia Regina","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Genetic and Biochemistry University of Uberl\u00e2ndia  Uberl\u00e2ndia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Trevisan","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmacology Federal University of Santa Maria  Santa Maria Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3797-8371","authenticated-orcid":false,"given":"Pierangelo","family":"Geppetti","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Clinical Pharmacology Unit University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9223-8395","authenticated-orcid":false,"given":"Romina","family":"Nassini","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Clinical Pharmacology Unit University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"De Logu","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Clinical Pharmacology Unit University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2960-5284","authenticated-orcid":false,"given":"Sara Marchesan","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Toxicological Biochemistry, Centre of Natural and Exact Sciences Federal University of Santa Maria  Santa Maria Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1548"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16178"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1179\/135100006X116628"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5369-07.2008"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.4081\/reumatismo.2021.1362"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12757"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1582432"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-10-18"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-003-0427-8"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2018.03.005"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000341664"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107959"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.06.036"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-01996-1"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.06.023"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0903442"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.734229"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2211631120"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)90144-9"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2019.11.006"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-10-40"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3266"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2015.03.014"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026915"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035677"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2918"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2008.12.010"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113241"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.04.037"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-019-0968-1"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-3326"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28204-z"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01739-2"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI128022"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02863-6"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00284"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.20.040180.002301"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00491"},{"key":"e_1_2_12_43_1","first-page":"313","article-title":"Protein peroxidation, magnesium deficiency and fibromyalgia","volume":"9","author":"Eisinger J.","year":"1996","journal-title":"Magnesium Research"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3758\/BF03193146"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11092462"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2020.104673"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4189"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.3791\/56337"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.22"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609598103"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/acupmed-2017-011395"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218329"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.075960"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000412"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2007.12.052"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000507"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-023-00922-6"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0b013e3182a0e383"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-018-0672-2"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209724"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy177"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-022-06407-5"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.216"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705924104"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-015-1716-2"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.05.024"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31827d415f"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-005-0079-y"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.02.003"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0350-23.2023"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14367"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2020.112643"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-00506-w"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3542-17.2018"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806919840098"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2020.1815191"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00158-2"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/smi.2648"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.108.054445"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00353"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001384"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww038"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705923104"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.5772\/intechopen.94492"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2005.12.009"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.96"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.118.248351"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-016-1808-1"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.22038\/ijbms.2020.39708.9408"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17715-1"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-020-4916-6"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2480-9"},{"key":"e_1_2_12_95_1","unstructured":"Leary S. Underwood W. Anthony R. Cartner S. Corey D. Grandin T. Greenacre C.B. Gwaltney\u2010Bran S. McCrackin M.A. Meyer R. Miller D. &Shearer J. Yanong R.[Internet]. (2020).AVMA guidelines for the euthanasia of animals. 2020 edition. [Cited 16 April 2020]. Available at:https:\/\/www.avma.org\/sites\/default\/files\/2020\u201001\/2020\u2010Euthanasia\u2010Final\u20101\u201017\u201020.pdf"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.16413","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T02:32:32Z","timestamp":1723170752000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.16413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,21]]},"references-count":94,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1111\/bph.16413"],"URL":"https:\/\/doi.org\/10.1111\/bph.16413","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,21]]},"assertion":[{"value":"2023-11-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}