title: Carvacrol attenuates mechanical hypernociception and inflammatory response.
abstract: Carvacrol is a phenolic monoterpene present in the essential oil of the family Lamiaceae, as in the genera Origanum and Thymus. We previously reported that carvacrol is effective as an analgesic compound in various nociceptive models, probably by inhibition of peripheral mediators that could be related with its strong antioxidant effect observed in vitro. In this study, the anti-hypernociceptive activity of carvacrol was tested in mice through models of mechanical hypernociception induced by carrageenan, and the involvement of important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF-α), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also investigated the anti-inflammatory effect of carvacrol on the model of carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide (LPS)-induced nitrite production in murine macrophages was observed. Systemic pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of mechanical hypernociception and edema induced by carrageenan and TNF-α; however, no effect was observed on hypernociception induced by PGE(2) and dopamine. Besides this, carvacrol significantly decreased TNF-α levels in pleural lavage and suppressed the recruitment of leukocytes without altering the morphological profile of these cells. Carvacrol (1, 10, and 100 μg/mL) also significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and did not produce citotoxicity in the murine peritoneal macrophages in vitro. The spontaneous locomotor activity of mice was not affected by carvacrol. This study adds information about the beneficial effects of carvacrol on mechanical hypernociception and inflammation. It also indicates that this monoterpene might be potentially interesting in the development of novel tools for management and/or treatment of painful conditions, including those related to inflammatory and prooxidant states.
authors.affiliation: Laboratório de Farmacologia Pré-Clinica, Departamento de Fisiologia, Universidade Federal de Sergipe (LAPEC/DFS/UFS), São Cristóvão, Sergipe, Brazil.
authors.forename: Adriana G
authors.initials: AG
authors.lastname: Guimarães
authors.forename: Maria A
authors.initials: MA
authors.lastname: Xavier
authors.forename: Marília T
authors.initials: MT
authors.lastname: de Santana
authors.forename: Enilton A
authors.initials: EA
authors.lastname: Camargo
authors.forename: Cliomar A
authors.initials: CA
authors.lastname: Santos
authors.forename: Fabíola A
authors.initials: FA
authors.lastname: Brito
authors.forename: Emiliano O
authors.initials: EO
authors.lastname: Barreto
authors.forename: Sócrates C H
authors.initials: SC
authors.lastname: Cavalcanti
authors.forename: Angelo R
authors.initials: AR
authors.lastname: Antoniolli
authors.forename: Rita C M
authors.initials: RC
authors.lastname: Oliveira
authors.forename: Lucindo J
authors.initials: LJ
authors.lastname: Quintans-Júnior
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002351:Carrageenan / Q000009:adverse effects; D002470:Cell Survival / Q000187:drug effects; D000081007:Cymenes; D015232:Dinoprostone / Q000009:adverse effects; D004298:Dopamine / Q000009:adverse effects; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000378:metabolism
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000081007:Cymenes; D008070:Lipopolysaccharides; D039821:Monoterpenes; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002351:Carrageenan; C073316:carvacrol; D015232:Dinoprostone; D004298:Dopamine