title: Central adenosine A1 and A2A receptors mediate the antinociceptive effects of neuropeptide S in the mouse formalin test.
abstract: OBJECTIVE
  The present study aimed to investigate the intraplantar (ipl) and central (icv) effects of neuropeptide S (NPS) in the formalin test and to evaluate the role of adenosine receptors, mainly A1 and A2A, in mediating such effects.
  
  
  METHODS
  The ipl injection of formalin was used to assess the nociceptive activity. Moreover, by pretreating mice with non-selective and selective antagonists of adenosine receptors, the effects of icv NPS on formalin-induced ongoing nociception were assessed.
  
  
  RESULTS
  Morphine-induced antinociceptive effects were observed during phases 1 and 2 of the test, while indomethacin was active only at the later nociceptive phase. The ipl injection of NPS (alone or combined with formalin) did not modify the nociceptive response. However, icv NPS significantly reduced formalin-induced nociception during both phases. Caffeine (3 mg/kg, ip), a non-selective adenosine receptor antagonist, prevented NPS-induced antinociceptive effects. Similar to caffeine, icv ZM241385 (0.01 nmol), an A2A receptor antagonist, prevented the antinociceptive effects of NPS. Moreover, icv DPCPX (0.001 nmol), an A1 receptor antagonist, blocked the effects of NPS only during phase 1.
  
  
  CONCLUSIONS
  The above findings suggest that: (i) NPS evokes central antinociceptive effects by activating both A1 and A2A receptors during phase 1, but (ii) only the adenosine A2A receptor during phase 2 of the formalin test.
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: A D Victor
authors.initials: AD
authors.lastname: Holanda
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Laila
authors.initials: L
authors.lastname: Asth
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Adair R
authors.initials: AR
authors.lastname: Santos
authors.affiliation: Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: de P Soares-Rachetti
authors.affiliation: Department of Medical Sciences, Section of Pharmacology, and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo'
authors.affiliation: Department of Pharmacology, Federal University of Parana, Curitiba, PR, Brazil.
authors.forename: Eunice
authors.initials: E
authors.lastname: André
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Electronic address: egavioli@hotmail.com.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Gavioli
mesh_terms: D000241:Adenosine / Q000737:chemistry; D000818:Animals; D005557:Formaldehyde / Q000737:chemistry; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000737:chemistry*; D059225:Nociception / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000502:physiology*
chemical_list: D009479:Neuropeptides; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; C539972:neuropeptide S, mouse; D005557:Formaldehyde; D000241:Adenosine
keywords: Adenosine antagonists; Formalin test; Mouse; Neuropeptide S; Nociception