title: TRP and ASIC channels mediate the antinociceptive effect of citronellyl acetate.
abstract: BACKGROUND
  Citronellyl acetate (CAT), a monoterpene product of the secondary metabolism of plants, has been shown in the literature to possess several different biological activities. However, no antinociceptive abilities have yet been discussed. Here, we used acute pain animal models to describe the antinociceptive action of CAT.
  
  
  METHODS
  The acetic acid-induced writhing test and the paw-licking test, in which paw licking was induced by glutamate and formalin, were performed to evaluate the antinociceptive action of CAT and to determine the involvement of PKC, PKA, TRPV1, TRPA1, TRPM8 and ASIC in its antinociceptive mechanism. To do so, we induced paw-linking using agonists.
  
  
  RESULTS
  CAT was administered intragastrically (25, 50, 75, 100 and 200 mg/kg), and the two higher doses caused antinociceptive effects in the acetic acid model; the highest dose reduced pain for 4h after it was administered (200 mg/kg). In the formalin test, two doses of CAT promoted antinociception in both the early and later phases of the test. The glutamate test showed that its receptors are involved in the antinociceptive mechanism of CAT. Pretreatment with CAT did not alter locomotor activity or motor coordination. In an investigation into the participation of TRP channels and ASICs in CAT's antinociceptive mechanism, we used capsaicin (2.2 μg/paw), cinnamaldehyde (10 mmol/paw), menthol (1.2 mmol/paw) and acidified saline (2% acetic acid, pH 1.98). The results showed that TRPV1, TRPM8 and ASIC, but not TRPA1, are involved in the antinociceptive mechanism. Finally, the involvement of PKC and PKA was also studied, and we showed that both play a role in the antinociceptive mechanism of CAT.
  
  
  CONCLUSIONS
  The results of this work contribute information regarding the antinociceptive properties of CAT on acute pain and show that, at least in part, TRPV1, TRPM8, ASIC, glutamate receptors, PKC and PKA participate in CAT's antinociceptive mechanism.
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, Brazil. emilianovasconcelos@yahoo.com.br
authors.forename: Emiliano Ricardo Vasconcelos
authors.initials: ER
authors.lastname: Rios
authors.forename: Nayrton Flávio Moura
authors.initials: NF
authors.lastname: Rocha
authors.forename: Alyne Mara Rodrigues
authors.initials: AM
authors.lastname: Carvalho
authors.forename: Leonardo Freire
authors.initials: LF
authors.lastname: Vasconcelos
authors.forename: Marília Leite
authors.initials: ML
authors.lastname: Dias
authors.forename: Damião Pergentino
authors.initials: DP
authors.lastname: de Sousa
authors.forename: Francisca Cléa Florenço
authors.initials: FC
authors.lastname: de Sousa
authors.forename: Marta Maria de França
authors.initials: MM
authors.lastname: Fonteles
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D062565:Acid Sensing Ion Channels / Q000187:drug effects* / Q000378:metabolism; D059787:Acute Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000284:Administration, Oral; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005121:Extremities / Q000473:pathology; D005557:Formaldehyde / Q000633:toxicity; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D059226:Nociceptive Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement; D045442:Rotarod Performance Test; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000378:metabolism
chemical_list: D062565:Acid Sensing Ion Channels; D000700:Analgesics; D039821:Monoterpenes; D050916:TRPV Cation Channels; D005557:Formaldehyde; C040879:citronellyl acetate; D019342:Acetic Acid