title: Tephrosia sinapou ethyl acetate extract inhibits inflammatory pain in mice: opioid receptor dependent inhibition of TNFα and IL-1β production.
abstract: CONTEXT. Tephrosia toxicaria is currently known as Tephrosia sinapou (Buc'hoz) A. Chev. (Fabaceae) and is a source of compounds such as flavonoids that inhibit inflammatory pain.
  
  
  OBJECTIVE
  To investigate the analgesic effect and mechanisms of the ethyl acetate extract of T. sinapou in inflammatory pain in mice.
  
  
  METHODS
  Behavioral responses were evaluated using mechanical (1-24 h) and thermal hyperalgesia (0.5-5 h), writhing response (20 min) and rota-rod (1-5 h) tests. Neutrophil recruitment (myeloperoxidase activity), cytokines (tumor necrosis factor [TNF]α and interleukin [IL]-1β), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels were determined by colorimetric assays. Pharmacological treatments were opioid receptor antagonist (naloxone, 0.1-1 mg/kg) and control opioid (morphine, 5 mg/kg). Inflammatory stimuli were carrageenin (100 µg/paw), complete Freund's adjuvant (CFA, 10 µl/paw), prostaglandin E2 (PGE2, 100 ng/paw) and acetic acid (0.8%).
  
  
  RESULTS
  The intraperitoneal pre-treatment with extract inhibited in a dose-dependent (30-300 mg/kg) dependent manner the mechanical hyperalgesia induced by carrageenin (up to 93% inhibition). The post-treatment (100 mg/kg) inhibited CFA-induced hyperalgesia (up to 63% inhibition). Naloxone (1 mg/kg) prevented the inhibitory effect of the extract over carrageenin-induced mechanical (100%) and thermal (100%) hyperalgesia, neutrophil recruitment (52%) and TNFα (63%) and IL-1β (98%) production, thermal threshold in naïve mice (99%), PGE2-induced mechanical hyperalgesia (88%) and acetic acid-induced writhing response (49%). There was no significant alteration in the rota-rod test, and AST and ALT serum levels by extract treatment. Discussion and conclusion. Tephrosia sinapou ethyl acetate extract reduces inflammatory pain by activating an opioid receptor-dependent mechanism.
authors.affiliation: Department of Pharmaceutical Sciences, University Hospital (Health Science Centre), Londrina State University, Parana, Brazil.
authors.forename: Renata M
authors.initials: RM
authors.lastname: Martinez
authors.forename: Ana C
authors.initials: AC
authors.lastname: Zarpelon
authors.forename: Renato D R
authors.initials: RD
authors.lastname: Cardoso
authors.forename: Fabiana T M C
authors.initials: FT
authors.lastname: Vicentini
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Georgetti
authors.forename: Marcela M
authors.initials: MM
authors.lastname: Baracat
authors.forename: Cesar C
authors.initials: CC
authors.lastname: Andrei
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Moreira
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
authors.forename: Rubia
authors.initials: R
authors.lastname: Casagrande
mesh_terms: D000085:Acetates / Q000737:chemistry; D000700:Analgesics / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D020556:Neutrophil Infiltration / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017288:Pain Threshold / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots; D010946:Plants, Medicinal; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012997:Solvents / Q000737:chemistry; D031304:Tephrosia / Q000737:chemistry; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000085:Acetates; D000700:Analgesics; D053583:Interleukin-1beta; D009292:Narcotic Antagonists; D010936:Plant Extracts; D011957:Receptors, Opioid; D012997:Solvents; D014409:Tumor Necrosis Factor-alpha; C007650:ethyl acetate