title: Oral treatment with essential oil of Hyptis spicigera Lam. (Lamiaceae) reduces acute pain and inflammation in mice: Potential interactions with transient receptor potential (TRP) ion channels.
abstract: BACKGROUND
  The genus Hyptis comprehends almost 400 species widespread in tropical and temperate regions of America. The use of Hyptis spicigera Lam. (Lamiaceae) is reported in traditional medicine due to its gastroprotective, anti-inflammatory and analgesic properties.
  
  
  OBJECTIVE
  The rationale of this study was to investigate the potential use of the essential oil of H. spicigera (EOHs) as analgesic.
  
  
  METHODS
  The antinociceptive effect of EOHs was verified analyzing acute nocifensive behavior of mice induced by chemical noxious stimuli [i.e., formalin and transient receptor potential (TRP) channels agonists]. We also verified the effects of EOHs on locomotor activity and motor performance in mice. Finally, we investigate the involvement of central afferent C-fibers with EOHs analgesic effect.
  
  
  RESULTS
  EOHs presented antinociceptive effect at 300 and 1000mg/kg on formalin-induced pain behavior model, presenting 50% and 72% of inhibition during the first phase (ED50=292mg/kg), and 85% and 100% during de second phase (ED50=205mg/kg), respectively. Temperature of the hind paw was reduced by EOHs treatment in a dose-dependent manner; oedema was diminished only by EOHs 1000mg/kg. EOHs does not impaired locomotor activity or motor performance. For mice injected with capsaicin, a TRPV1 activator, EOHs (1000mg/kg, ED50=660mg/kg) showed decreased (63%) nociceptive behavior. When injected with cinnamaldehyde (TRPA1 activator), mice treated with EOHs showed 23%, 43% and 66% inhibition on nociceptive behavior (100, 300 and 1000mg/kg, respectively; ED50402mg/kg). When mice were injected with menthol (TRPM8 activator), EOHs showed 29%, 59% and 98% inhibition of nociceptive behavior (100, 300 and 1000mg/kg, respectively; with ED50=198mg/kg. Finally, when desensitized mice were injected with menthol, EOHs (300mg/kg) does not show antinociceptive effect.
  
  
  CONCLUSIONS
  This study demonstrated the efficacy of EOHs on experimental models of nociception. We have found the involvement of TRP channels V1, A1 and M8 with EOHs activity, which was remarkably potent and efficient in inhibiting pain evoked by menthol, a TRPM8 channel activator. TRPM8 channels from TRPV1+ C-fibers, but not TRPM8+ C-fibers nor TRPM8+ Aδ mechanosensory fibers, mediate EOHs analgesic effects.
authors.affiliation: Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil; Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil.
authors.forename: Róli Rodrigues
authors.initials: RR
authors.lastname: Simões
authors.affiliation: Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil; Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil.
authors.forename: Igor Dos Santos
authors.initials: ID
authors.lastname: Coelho
authors.affiliation: Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil; Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil.
authors.forename: Stella Célio
authors.initials: SC
authors.lastname: Junqueira
authors.affiliation: Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil.
authors.forename: Glauce Regina
authors.initials: GR
authors.lastname: Pigatto
authors.affiliation: Departamento de Biologia Vegetal, Universidade Estadual de Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Marcos José
authors.initials: MJ
authors.lastname: Salvador
authors.affiliation: Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil; Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Florianópolis, Santa Catarina, Brazil. Electronic address: adair.santos@ufsc.br.
authors.forename: Adair Roberto Soares
authors.initials: AR
authors.lastname: Santos
authors.affiliation: Departamento de Biologia Vegetal, Universidade Estadual de Campinas - UNICAMP, Campinas, São Paulo, Brazil. Electronic address: defaria.felipe@gmail.com.
authors.forename: Felipe Meira
authors.initials: FM
authors.lastname: de Faria
mesh_terms: D059787:Acute Pain / Q000188:drug therapy* / Q000378:metabolism; D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage* / Q000302:isolation & purification; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D005260:Female; D031331:Hyptis; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D019686:Lamiaceae; D051379:Mice; D009822:Oils, Volatile / Q000008:administration & dosage* / Q000302:isolation & purification; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D050051:Transient Receptor Potential Channels / Q000819:agonists* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D009822:Oils, Volatile; D050051:Transient Receptor Potential Channels