title: Involvement of endogenous opioid peptides in the peripheral antinociceptive effect induced by the coffee specific diterpene kahweol.
abstract: BACKGROUND
  Kahweol is a diterpene present in the oil derived from coffee beans. Although several pharmacological activities of kahweol are already well described in the literature, no study was done in order to assess the analgesic activity of this substance. Thus, the aim of this study was to investigate the possible peripheral antinociceptive effect of kahweol. Considering that the opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, the present study also evaluated the endogenous opioids involvement in this effect.
  
  
  METHODS
  The rat paw pressure test was used, and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2μg/paw). All drugs were administered subcutaneously in the hindpaws of male Wistar rats. The expression of β-endorphin was examined by immunohistochemistry in the skin tissue samples of the plantar surface of rat right hindpaws.
  
  
  RESULTS
  Intraplantar injection of kahweol (40 and 80μg) induced significant peripheral antinociception. The antinociceptive effect of kahweol was due to a local peripheral action because the higher dose (80μg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (50 and 100μg/paw) prevented action of kahweol (80μg/paw) and the aminopeptidases inhibitor bestatin (400μg/paw) potentiated the antinociceptive effect of kahweol (40μg/paw). Furthermore, kahweol treatment increased the intensity of β-endorphin immunoreactivity in the epithelium of rat paws.
  
  
  CONCLUSIONS
  The results discussed here provide evidence that kahweol treatment has peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Luciana S
authors.initials: LS
authors.lastname: Guzzo
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Thiago R L
authors.initials: TR
authors.lastname: Romero
authors.affiliation: Department of Pathology, Institute of Biological Sciences, ICB-UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Celso M
authors.initials: CM
authors.lastname: Queiroz-Junior
authors.affiliation: Department of Pathology, Institute of Biological Sciences, ICB-UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Marcelo V
authors.initials: MV
authors.lastname: Caliari
authors.affiliation: Department of Pharmacology, UNILAVRAS, Lavras, MG, Brazil.
authors.forename: Adolfo O
authors.initials: AO
authors.lastname: Azevedo
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Andréa C
authors.initials: AC
authors.lastname: Perez
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Belo Horizonte, MG, Brazil. Electronic address: dimitri@icb.ufmg.br.
authors.forename: Igor D G
authors.initials: ID
authors.lastname: Duarte
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003069:Coffee / Q000737:chemistry*; D015232:Dinoprostone; D004224:Diterpenes / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010147:Pain Measurement; D010455:Peptides / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D001615:beta-Endorphin / Q000096:biosynthesis
chemical_list: D000700:Analgesics; D003069:Coffee; D004224:Diterpenes; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010455:Peptides; D009270:Naloxone; D001615:beta-Endorphin; C053401:kahweol; D007930:Leucine; C012211:ubenimex; D015232:Dinoprostone
keywords: Coffee diterpene; Kahweol; Opioid system; Peripheral antinociception; β-Endorphin