title: TRPV1 channel inhibition contributes to the antinociceptive effects of Croton macrostachyus extract in mice.
abstract: BACKGROUND
  Previous study showed that extracts from Croton macrostachyus (Euphorbiaceae) exhibit analgesic effects in acute pain models. The present study evaluates the antinociceptive properties of the methanol/methylene chloride extract (MECM) of the stem bark of this plant using mice models of persistent inflammatory and neuropathic pain, and assesses its mechanism of action.
  
  
  METHODS
  MECM was tested on Complete Freund adjuvant (CFA)-induced persistent thermal and mechanical pain, neuropathic pain induced by partial sciatic nerve ligation (PSNL), prostaglandin E2 (PGE2)-induced acute mechanical hyperalgesia, as well as on nociception induced by capsaicin in mice. Mechanical hyperalgesia was assessed using von Frey hair in awake mice. The mechanism of action of MECM was evaluated by using glibenclamide on PGE2-induced hyperalgesia or rimonabant on capsaicin-induced pain.
  
  
  RESULTS
  MECM administered orally at the doses of 250 and 500 mg/kg, induced long lasting and significant antihyperalgesic effects on CFA-inflammatory and PSNL-induced neuropathic pain. MECM significantly reduced the mechanical hyperalgesia induced by PGE2 either when administered preventively or therapeutically. MECM also significantly and time dependently inhibited the capsaicin-induced nociception. These effects were not affected by glibenclamide or by rimonabant.
  
  
  CONCLUSIONS
  The present results demonstrate that the oral administration of MECM to mice resulted in long lasting antihyperalgesic activity in inflammatory and neuropathic pain as well as in acute and persistent pain. The mechanism underlying the long lasting MECM antihyperalgesic effect is currently unknown, but might be mediated, at least partially, through the modulation of TRPV1 receptors.
authors: Laboratory of Animal Physiology and Phytopharmacology, Department of Animal Biology, Faculty of Sciences, University of Dschang, P.O. Box 67, Dschang, Cameroon. nguelefack@yahoo.fr.|Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina UFSC, Campus Universitario, Rua Ferreira Lima 82, Trindade, 88049-900, Florianopolis, SC, Brazil. nguelefack@yahoo.fr.
authors: Télesphore Benoît
authors: TB
authors: Nguelefack
authors: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina UFSC, Campus Universitario, Rua Ferreira Lima 82, Trindade, 88049-900, Florianopolis, SC, Brazil. rafaeldutra@gmail.com.|Laboratory of Autoimmunity and Immunopharmacology, Campus Araranguá, Universidade Federal de Santa Catarina, 88900-000, Araranguá, SC, Brazil. rafaeldutra@gmail.com.
authors: Rafael Cypriano
authors: RC
authors: Dutra
authors: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina UFSC, Campus Universitario, Rua Ferreira Lima 82, Trindade, 88049-900, Florianopolis, SC, Brazil. ana-dear@yahoo.com.br.
authors: Ana Flavia
authors: AF
authors: Paszcuk
authors: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina UFSC, Campus Universitario, Rua Ferreira Lima 82, Trindade, 88049-900, Florianopolis, SC, Brazil. edineialemos@ig.com.br.
authors: Edinéia Lemos
authors: EL
authors: de Andrade
authors: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina UFSC, Campus Universitario, Rua Ferreira Lima 82, Trindade, 88049-900, Florianopolis, SC, Brazil. calixto@farma.ufsc.br.|Centre of inovation and preclinic studies (CIEnP), Av. Luiz Boiteux Piazza 1302, Cachoeira do Bom Jesus, Florianópolis, SC, Brazil. calixto@farma.ufsc.br.
authors: João Batista
authors: JB
authors: Calixto
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002211:Capsaicin / Q000009:adverse effects; D029802:Croton / Q000737:chemistry*; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology; D010936:Plant Extracts / Q000494:pharmacology*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
chemical_list: D000700:Analgesics; D010936:Plant Extracts; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D002211:Capsaicin