Role of kinin receptors B1 and B2 in the generation and inhibition of pain

• Antragstellerin: Dr. Cécile Cayla
• Fachliche Zuordnung: Anästhesiologie
• Förderung: Förderung von 2008 bis 2011
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 62604774

Kinins that are produced in response to tissue trauma and inflammation, are involved in the initiation of pain and in the development of hypersensitivity of damaged tissues. Kinins act through two G protein coupled receptors named B1 and B2. The constitutively expressed B2 receptor appears to be involved in acute phases and the injury-induced B1 receptor in chronic phases of inflammatory and pain responses. The overall contribution and importance of kinins in painful processes is not completely understood in vivo. Recently, we generated mice lacking both kinin receptors (B1/B2KO). This is the first animal model completely unresponsive to kinins in in vitro assays and therefore enables us to study the full relevance of kinin receptors in painful processes. In this study, our first goal is to investigate the contribution of kinins acting through B1 and B2 receptors in pain. This will be done by analysing the nociceptive behaviour of B1/B2KO animals in tests covering basal nociception, inflammatory pain, and neuropathic pain. Since recent studies showed that bradykinin can influence opioid receptor function, our second goal is to test whether kinins are involved in the enhancement of peripheral opioid antinociception associated with inflammation and injury. Taking advantage of the B1/B2KO model we will examine mechanisms of interaction between the kinin and opioid systems during injury in vivo, and in isolated sensory neurons in vitro. A better understanding of the modulation of hyperalgesic and antihyperalgesic mechanisms by kinin receptors is the overall aim of our project.

• DFG-Verfahren: Sachbeihilfen