title: Impaired nociception and peripheral opioid antinociception in mice lacking both kinin B1 and B2 receptors.
abstract: BACKGROUND
  Kinins (e.g., bradykinin) acting through the constitutively expressed B2 and the injury-induced B1 receptors are involved in pain and hyperalgesia, as previously shown by use of receptor-selective antagonists and single-receptor knockout models. Because the overall contribution of kinins to painful processes remains unclear, the aim of this study was to analyze pain-related behaviors of mice unable to respond to kinins because of a lack of both B1 and B2 receptors.
  
  
  METHODS
  In knockout mice lacking both B1 and B2 receptors and in wild-type mice (n = 8-21 per group) the authors assessed nociceptive thresholds to mechanical and heat stimuli (von Frey and Hargreaves tests, respectively) in healthy animals and after induction of inflammatory and neuropathic pain, acid-induced visceral nociception, and modulation of nociceptive responses by peripherally administered opioid agonists.
  
  
  RESULTS
  In knockout mice lacking both B1 and B2 receptors baseline nociceptive responses to heat were unaltered, nocifensive responses to bradykinin were abolished, acute acetic acid-induced visceral nociception was reduced by approximately 70% (mean difference: 19.5 writhes/30 min) and heat hypersensitivity in carrageenan-induced paw inflammation was decreased 48 h after injection (mean difference 2.88 s), hypersensitivities in chronic complete Freund's adjuvant-induced paw inflammation or after chronic constriction injury of the sciatic nerve were unchanged, and peripheral μ- and δ-opioid-induced analgesia after chronic constriction injury was reduced by 30-35% (mean differences: μ-agonist: 0.495 g, δ-agonist: 0.555 g).
  
  
  CONCLUSIONS
  These data suggest that kinins are important for nociception associated with acute short-lasting inflammation but are less essential in chronic stages of pain. The results also highlight a new protective function of kinins via interactions with the opioid system.
authors.affiliation: Klinik für Anaesthesiologie und Operative Intensivmedizin, Campus Benjamin Franklin, Berlin, Germany. cecile.cayla@charite.de
authors.forename: Cecile
authors.initials: C
authors.lastname: Cayla
authors.forename: Dominika
authors.initials: D
authors.lastname: Labuz
authors.forename: Halina
authors.initials: H
authors.lastname: Machelska
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfer
authors.forename: Christoph
authors.initials: C
authors.lastname: Stein
mesh_terms: D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D043783:Receptor, Bradykinin B1 / Q000819:agonists / Q000172:deficiency*; D043782:Receptor, Bradykinin B2 / Q000819:agonists / Q000172:deficiency*; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2