Impaired nociception and peripheral opioid antinociception in mice lacking both kinin b1 and b2 receptors

Item Type:	Article
Title:	Impaired nociception and peripheral opioid antinociception in mice lacking both kinin b1 and b2 receptors
Creators Name:	Cayla, C. and Labuz, D. and Machelska, H. and Bader, M. and Schaefer, M. and Stein, C.
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 Mu- and d-opioid-induced analgesia after chronic constriction injury was reduced by 30-35% (mean differences: Mu-agonist: 0.495 g, d-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.
Keywords:	Bradykinin B1 Receptor, Bradykinin B2 Receptor, Inbred C57BL Mice, Knockout Mice, Nociception, Opioid Analgesics, Sciatic Neuropathy, Animals, Mice
Source:	Anesthesiology
ISSN:	0003-3022
Publisher:	Lippincott Williams & Wilkins
Volume:	116
Number:	2
Page Range:	448-457
Date:	February 2012
Official Publication:	https://doi.org/10.1097/ALN.0b013e318242b2ea
PubMed:	View item in PubMed

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