title: m-Trifluoromethyl-diphenyl diselenide, a multi-target selenium compound, prevented mechanical allodynia and depressive-like behavior in a mouse comorbid pain and depression model.
abstract: Chronic pain and depression are two complex states that often coexist in the clinical setting and traditional antidepressants and analgesics have shown limited clinical efficacy. There is an intricate communication between the immune system and the central nervous system and inflammation has been considered a common mediator of pain-depression comorbidity. This study evaluated the effect of m-trifluoromethyl diphenyl diselenide [(m-CF3-PhSe)2], an organoselenium compound that has been reported to have both antinociceptive and antidepressant-like actions, in the comorbidity of chronic pain and depression induced by partial sciatic nerve ligation (PSNL) in an inflammatory approach. Mice were submitted to PSNL during 4weeks and treated with (m-CF3-PhSe)2 acutely (0.1-10mg/kg, i.g.) or subchronically (0.1mg/kg, i.g., once a day during the 3rd and 4th weeks). Both treatments prevented PSNL-increased pain sensitivity and depressive-like behavior observed in Von-Frey hair (VFH) and forced swimming (FST) tests, respectively. These effects could be mainly associated with an anti-inflammatory action of (m-CF3-PhSe)2 which reduced the levels of pro-inflammatory cytokines, NF-κB and COX-2, and p38 MAPK activation that were increased by PSNL. (m-CF3-PhSe)2 also increased the BDNF levels and reduced glutamate release and 5-HT uptake altered by PSNL. Although acute and subchronic treatments with (m-CF3-PhSe)2 prevented these alterations induced by PSNL, the best results were found when (m-CF3-PhSe)2 was subchronically administered to mice. Considering the potential common mechanisms involved in the comorbidity of inflammation-induced depression and chronic pain, the results found in this study indicate that (m-CF3-PhSe)2 could become an interesting molecule to treat long-lasting pathological pain associated with depression.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: César Augusto
authors.initials: CA
authors.lastname: Brüning
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: Franciele
authors.initials: F
authors.lastname: Martini
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: Suelen Mendonça
authors.initials: SM
authors.lastname: Soares
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: Tuane Bazanella
authors.initials: TB
authors.lastname: Sampaio
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil.
authors.forename: Bibiana Mozzaquatro
authors.initials: BM
authors.lastname: Gai
authors.affiliation: Departamento de Ciências da Saúde, Universidade Luterana do Brasil, Santa Maria, Rio Grande do Sul, Brazil.
authors.forename: Marta M M F
authors.initials: MM
authors.lastname: Duarte
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil. Electronic address: criswn@ufsm.br.
authors.forename: Cristina Wayne
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood; D003863:Depression / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D007839:Functional Laterality; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000150:complications* / Q000209:etiology / Q000523:psychology*; D017646:Organosilicon Compounds / Q000627:therapeutic use*; D059348:Peripheral Nerve Injuries / Q000150:complications; D012701:Serotonin / Q000378:metabolism; D013550:Swimming / Q000523:psychology; D013574:Synaptosomes / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D016207:Cytokines; D017646:Organosilicon Compounds; C546861:m-trifluoromethyl-diphenyl diselenide; D014316:Tritium; D012701:Serotonin; D018698:Glutamic Acid; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: Depression; Inflammation; Neuropathic pain; Selenium; p38 MAPK