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Impaired nociception and peripheral opioid antinociception in mice lacking both kinin b1 and b2 receptors.
MedLine Citation:
PMID:  22273860     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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:
Cecile Cayla; Dominika Labuz; Halina Machelska; Michael Bader; Michael Schäfer; Christoph Stein
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anesthesiology     Volume:  116     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  448-57     Citation Subset:  AIM; IM    
Affiliation:
* Principal Scientist, † Scientist, ‡ Professor, # Chair, Klinik für Anaesthesiologie und Operative Intensivmedizin, Campus Benjamin Franklin, Berlin, Germany. § Professor, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. ‖ Current position: Professor, Campus Virchow Klinikum, Charité-Universitätsmedizin, Berlin, Germany.
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