title: Antinociceptive effect of Mirabilis jalapa on acute and chronic pain models in mice.
abstract: BACKGROUND
  The infusion or decoction of Mirabilis jalapa leaves is used in traditional medicine in Brazil to treat inflammatory and painful diseases. Thus, the present study was designed to investigate whether the leaf ethyl acetate (Eta) fraction from Mirabilis jalapa exhibits antinociceptive effect in clinically relevant pain models in mice. Furthermore, we have investigated the role of cholinergic system in the antinociceptive action produced by Eta in mice.
  
  
  METHODS
  The effect of Eta administered orally (10mg/kg, p.o.) in mice was verified on the painful hypersensitivity (mechanical allodynia) in models of chronic inflammation (subcutaneous injection of complete Freund's Adjuvant-CFA in the plantar surface of the right hind paw), postoperative (paw surgical incision) and neuropathic (partial sciatic nerve ligation) pain. In the chronic inflammation model, we further verified the effect of Eta treatment on paw edema and interleukin-1β (IL-1β) levels. We also investigated the role of muscarinic and nicotinic receptors in the antiallodynic action produced by Eta as well as the possible action of Eta on in vitro and ex vivo acetylcholinesterase activity in CFA treated animals. Furthermore, we verified the effect of Eta treatment on the parameters of liver and kidney lesion (level of urea, and activity of aspartate aminotransferase and alanine aminotransferase).
  
  
  RESULTS
  Eta produced marked reduction in the allodynia caused by CFA, surgical incision and partial sciatic nerve ligation. However, Eta did not alter the paw edema or the increase of IL-1β levels produced by CFA. The antinociceptive effect of Eta was reversed by the pre-treatment of animals with the antagonists of muscarinic (atropine, 5mg/kg, s.c) or nicotinic (mecamylamine, 0.001mg/kg, s.c.) receptors. Eta did not alter in vitro acetylcholinesterase activity in blood or spinal cord samples, but it reversed the increase in the acetylcholinesterase activity observed in the spinal cord samples from mice injected with CFA. Moreover, Eta did not alter the indicators of liver or kidney lesion.
  
  
  CONCLUSIONS
  Based on its use in traditional medicine, the results of the present study confirmed the antinociceptive properties of Eta in clinically relevant pain models. Also its effect on the CFA-induced chronic inflammation seems to be related to acetylcholinesterase inhibition and cholinergic system.
authors.affiliation: Departamento de Saúde, Curso de Farmácia, Universidade Federal de Sergipe, SE, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. Electronic address: bandewalk@hotmail.com.
authors.forename: Cristiani I B
authors.initials: CI
authors.lastname: Walker
authors.forename: Gabriela
authors.initials: G
authors.lastname: Trevisan
authors.forename: Mateus F
authors.initials: MF
authors.lastname: Rossato
authors.forename: Cássia R
authors.initials: CR
authors.lastname: Silva
authors.forename: Franciele V
authors.initials: FV
authors.lastname: Pinheiro
authors.forename: Carina
authors.initials: C
authors.lastname: Franciscato
authors.forename: Etiane
authors.initials: E
authors.lastname: Tatsch
authors.forename: Maria B
authors.initials: MB
authors.lastname: Moretto
authors.forename: Morgana D
authors.initials: MD
authors.lastname: Silva
authors.forename: Melânia P
authors.initials: MP
authors.lastname: Manfron
authors.forename: Rafael
authors.initials: R
authors.lastname: Noal Moresco
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
authors.forename: Maria E
authors.initials: ME
authors.lastname: Pereira
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D059787:Acute Pain / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D000700:Analgesics / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D059350:Chronic Pain / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D006930:Hyperalgesia / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008297:Male; D051379:Mice; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D018515:Plant Leaves / Q000737:chemistry; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology
chemical_list: D000700:Analgesics; D053583:Interleukin-1beta; D010936:Plant Extracts; D000110:Acetylcholinesterase
keywords: AChE; ALT; AST; Acetylcholinesterase; Antinociceptive; CFA; Eta; IL-1β; M. jalapa; Mirabilis jalapa; Muscarinic; Nicotinic; Nyctaginaceae; Pain; alanine aminotransferase; aspartate aminotransferase; complete Freund’s Adjuvant; i.p.; interleukin-1β; intraperitoneal administration; oral administration; p.o.; s.c.; subcutaneous route; the leaf ethyl acetate fraction from Mirabilis jalapa