title: Effects of D-series resolvins on behavioral and neurochemical changes in a fibromyalgia-like model in mice.
abstract: This study investigated whether the spinal or systemic treatment with the lipid resolution mediators resolvin D1 (RvD1), aspirin-triggered resolvin D1 (AT-RvD1) and resolvin D2 (RvD2) might interfere with behavioral and neurochemical changes in the mouse fibromyalgia-like model induced by reserpine. Acute administration of AT-RvD1 and RvD2 produced a significant inhibition of mechanical allodynia and thermal sensitization in reserpine-treated mice, whereas RvD1 was devoid of effects. A similar antinociceptive effect was obtained by acutely treating animals with the reference drug pregabalin. Noteworthy, the repeated administration of AT-RvD1 and RvD2 also prevented the depressive-like behavior in reserpine-treated animals, according to assessment of immobility time, although the chronic administration of pregabalin failed to affect this parameter. The induction of fibromyalgia by reserpine triggered a marked decrease of dopamine and serotonin (5-HT) levels, as examined in total brain, spinal cord, cortex and thalamus. Reserpine also elicited a reduction of glutamate levels in total brain, and a significant increase in the spinal cord and thalamus. Chronic treatment with RvD2 prevented 5-HT reduction in total brain, and reversed the glutamate increases in total brain and spinal cord. Otherwise, AT-RvD1 led to a recovery of dopamine levels in cortex, and 5-HT in thalamus, whilst it diminished brain glutamate contents. Concerning pregabalin, this drug prevented dopamine reduction in total brain, and inhibited glutamate increase in brain and spinal cord of reserpine-treated animals. Our data provide novel evidence, showing the ability of D-series resolvins AT-RvD1, and mainly RvD2, in reducing painful and depressive symptoms allied to fibromyalgia in mice.
authors.affiliation: Postgraduate Program in Cellular and Molecular Biology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Caroline P
authors.initials: CP
authors.lastname: Klein
authors.affiliation: Faculty of Pharmacy, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Nathalia D M
authors.initials: ND
authors.lastname: Sperotto
authors.affiliation: Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Izaque S
authors.initials: IS
authors.lastname: Maciel
authors.affiliation: Institute of Toxicology and Pharmacology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Leite
authors.affiliation: Institute of Toxicology and Pharmacology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Alessandra H
authors.initials: AH
authors.lastname: Souza
authors.affiliation: Postgraduate Program in Cellular and Molecular Biology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Institute of Toxicology and Pharmacology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil; School of Dentistry, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: camposmmartha@yahoo.com.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D005356:Fibromyalgia / Q000188:drug therapy* / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D051379:Mice; D059226:Nociceptive Pain / Q000188:drug therapy / Q000503:physiopathology; D000069583:Pregabalin; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology; D014110:Touch; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000928:Antidepressive Agents; C518399:resolvin D1; C545423:resolvin D2; D004281:Docosahexaenoic Acids; D012701:Serotonin; D018698:Glutamic Acid; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D004298:Dopamine
keywords: D-series resolvins; Fibromyalgia; Mice; Neurotransmitters; Pregabalin; Reserpine