title: Anti-nociceptive, anti-hyperalgesic and anti-arthritic activity of amides and extract obtained from Piper amalago in rodents.
abstract: BACKGROUND
  Piper amalago (Piperaceae) has been used in folk medicine as an analgesic. This study aimed to evaluate the pharmacological effects of extract and pure amides obtained from P. amalago on pain to provide a pharmacological basis for their use in traditional medicine.
  
  
  OBJECTIVE
  This study evaluated the anti-nociceptive, anti-hyperalgesic, anti-arthritic and anti-depressive activities of the ethanolic extract of P. amalago (EEPA) and the amides N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine (1) and N-[7-(3',4'-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl] pyrrolidine (2) obtained from P. amalago in animal models.
  
  
  METHODS
  Mice treated daily with EEPA (100mg/kg, p.o.) were assayed for 20 days for knee edema (micrometer measurement), mechanical hyperalgesia (analgesiometer analysis), heat sensitivity and immobility (forced swim test) in the Complete Freund's Adjuvant (CFA) model. Cold (acetone test) and mechanical hyperalgesia (electronic von Frey analysis) responses were evaluated for 15 days in rats treated with oral EEPA (100mg/kg) in the spared nerve injury (SNI) model. Meanwhile, mice were evaluated for carrageenan-induced edema and mechanical hyperalgesia and for nociception using the formalin model after a single administration of EEPA (100mg/kg) or amides 1 and 2 (1mg/kg).
  
  
  RESULTS
  Amides (1) and (2) were detected and isolated from the EEPA. The EEPA inhibited mechanical hyperalgesia, knee edema, and heat hyperalgesia, but not depressive-like behavior, induced by the intraplantar injection of CFA. When evaluated in the SNI model, the EEPA inhibited mechanical and cold hyperalgesia. The EEPA, 1 and 2 prevented the mechanical hyperalgesia induced by carrageenan and the anti-nociceptive effects in both phases of formalin nociception. The EEPA did not induce alterations in the open field test.
  
  
  CONCLUSIONS
  The EEPA was effective for inhibition of pain and arthritic parameters but was not effective against depressive-like behavior; additionally, it did not alter locomotor activity. The amides obtained seemed to be the active component(s) present in the EEPA because they proved to be anti-nociceptive and anti-hyperalgesic in models of acute pain. Considering that few drugs are currently available for the treatment of chronic pain, especially neuropathic pain, the present results may have clinical relevance and open new possibilities for the development of new anti-hyperalgesic and anti-arthritic agents from P. amalago.
authors.affiliation: College of Health Science, Federal University of Grande Dourados, Dourados, MS, Brazil.
authors.forename: Jucicléia
authors.initials: J
authors.lastname: da Silva Arrigo
authors.affiliation: College of Health Science, Federal University of Grande Dourados, Dourados, MS, Brazil.
authors.forename: Eloise
authors.initials: E
authors.lastname: Balen
authors.affiliation: College of Health Science, Federal University of Grande Dourados, Dourados, MS, Brazil.
authors.forename: Ubirajara Lanza
authors.initials: UL
authors.lastname: Júnior
authors.affiliation: Chemistry Department, State University of Grande Dourados, MS, Brazil.
authors.forename: Jonas
authors.initials: J
authors.lastname: da Silva Mota
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), 13084-971 Campinas, SP, Brazil.
authors.forename: Renan Donomae
authors.initials: RD
authors.lastname: Iwamoto
authors.affiliation: Department of Chemistry, Polytechnic Center, Federal University of Paraná Federal University, Curitiba, PR, Brazil.
authors.forename: Andersson
authors.initials: A
authors.lastname: Barison
authors.affiliation: Institute of Health Science, Federal University of Mato Grosso, Brazil.
authors.forename: Mario Mateus
authors.initials: MM
authors.lastname: Sugizaki
authors.affiliation: College of Health Science, Federal University of Grande Dourados, Dourados, MS, Brazil. Electronic address: candida2005@gmail.com.
authors.forename: Cândida Aparecida
authors.initials: CA
authors.lastname: Leite Kassuya
mesh_terms: D000577:Amides / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy*; D003080:Cold Temperature; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D006930:Hyperalgesia / Q000188:drug therapy*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000523:psychology; D013550:Swimming / Q000523:psychology
chemical_list: D000577:Amides; D000700:Analgesics; D000928:Antidepressive Agents; D010936:Plant Extracts
keywords: Amides; Chronic inflammation; Hyperalgesia; Piper amalago; Piperaceae