Role of kinin receptors B1 and B2 in the generation and inhibition of pain
Final Report Abstract
Kinins are kininogen-derived small peptides rapidly produced at the site of tissue injury or inflammation and they are important in the initiation of pain and the exaggeration of sensory signalling (hypersensitivity) in damaged tissues. They act through two G protein coupled receptors, the injury-induced B1 receptor and the constitutive B2 receptor. A promising therapeutic application of kinin receptor antagonists is analgesia. The overall aim of our research was to better understand the modulation of hyperalgesic and antihyperalgesic mechanisms by kinin receptors. We analysed for the first time pain behaviours of mice unable to respond to kinins, due to lack of both kinin receptors (B1/B2KO mice). Tests examining basal nociception, inflammatory pain, and neuropathic pain were performed. Our results show that kinins are important for nociception associated with acute short lasting inflammation but are not essential in the development of more chronic stages of pain in mice. Our research also highlighted a new protective function of kinins via interactions with the opioid system in vivo since the B1/B2KO animals presented lower analgesic responses to peripherally applied opioids. The findings of this research gave essential information regarding the role of endogenously produced kinins in painful processes. This is critical as the use of classical pain-killers like opioid and non steroidal anti-inflammatory drugs are limited by severe side effects and there is a need for alternatives to the currently available drugs.
Publications
-
Impaired nociception and peripheral opioid antinociception in mice lacking both kinin B1 and B2 receptors. Anesthesiology. 2012 Feb; 116(2): 448-57
Cayla, Cecile; Labuz, Dominika; Machelska, Halina; Bader, Michael; Schäfer, Michael & Stein, Christoph
