title: Oral treatment with methanolic extract of the root bark of Condalia buxifolia Reissek alleviates acute pain and inflammation in mice: Potential interactions with PGE2, TRPV1/ASIC and PKA signaling pathways.
abstract: BACKGROUND
  The Condalia buxifolia root bark infusion is used in traditional medicine in Brazil as antipyretic, anti-inflammatory and anti-dysentery. Previous data from our group showed that methanolic extract of Condalia buxifolia (MECb) produced a marked antinociceptive effect in animal models of acute pain. The purpose of this study was to investigate the mechanisms of MECb-induced antinociception as measured by nocifensive behavior in pain induced by endogenous (prostaglandin E2) or exogenous (TRPs and ASIC agonist, and protein kinase A and C activators) chemical stimuli, and the potential role of PKA signaling and capsaicin-sensitive central C-fiber afferents.
  
  
  METHODS
  The effect of MECb administered orally (0.1-300mg/kg, i.g.) to mice on nociception induced by capsaicin (TRPV1 agonist), cinnamaldehyde (TRPA1 agonist), menthol (TRPM8 agonist), acidified saline (ASIC agonist), PMA (protein kinase C activator), PGE2 and forskolin (protein kinase A activator) was assessed. Moreover, this study also investigated the role of C-fibers desensitizing mice with a high dose of intrathecal capsaicin. Furthermore, this study performed the western blot to PKA phosphorylated on nocifensive behavior induced by forskolin.
  
  
  RESULTS
  MECb was able to reduce the nociception and paw edema induced by capsaicin, acidified saline, PMA, PGE2 and forskolin, but not by cinnamaldehyde or menthol. Western blot analyses showed that MECb reduced the levels of PKA phosphorylation induced by forskolin in hind paws. Finally, ablating central afferent C-fibers abolished MECb antinociception.
  
  
  CONCLUSIONS
  In accordance with its use in traditional medicine, these findings provide new evidence indicating that Condalia buxifolia reduces the acute painful behavior of animals caused by chemical stimuli. The precise mechanism of MECb antinociceptive activity is not completely understood but the results suggest involvement of PGE2, TRPV1/ASIC and PKA signaling pathways, and require integrity of the capsaicin-sensitive central C-fiber afferents.
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil; Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil; Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Róli Rodrigues
authors.initials: RR
authors.lastname: Simões
authors.affiliation: Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Igor
authors.initials: I
authors.lastname: Dos Santos Coelho
authors.affiliation: Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Caroline Cunha
authors.initials: CC
authors.lastname: do Espírito Santo
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, SC, Brazil.
authors.forename: Ademir Farias
authors.initials: AF
authors.lastname: Morel
authors.affiliation: Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Eliane Maria
authors.initials: EM
authors.lastname: Zanchet
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil; Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: adair.santos@ufsc.br.
authors.forename: Adair Roberto Soares
authors.initials: AR
authors.lastname: Santos
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism; D000284:Administration, Oral; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement; D008517:Phytotherapy; D024301:Plant Bark / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D027823:Rhamnaceae / Q000737:chemistry*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone
keywords: ASIC; Acute pain; Condalia Buxifolia; PKA; PKC; TRPV1