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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.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Cayla C,Labuz D,Machelska H,Bader M,Schäfer M,Stein C

doi

10.1097/ALN.0b013e318242b2ea

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

448-57

issue

eissn

0003-3022

issn

1528-1175

pii

00000542-201202000-00029

journal_volume

116

pub_type

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Impaired nociception and peripheral opioid antinociception in mice lacking both kinin B1 and B2 receptors.