Sensory TRP channel complexes in pain transduction and inflammatory hypersensitivity

• Applicant: Dr. Marian Brackmann
• Subject Area: Pharmacology
• Term: from 2008 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 73194157

Noxious thermal, mechanical, or chemical stimuli evoke pain through excitation of peripheral terminals of sensory neurons called nociceptors. In addition to mediating pain these neurons contribute to tissue inflammation via a mechanism called neurogenic inflammation. Prolonged activation of sensory nerve terminals leads to the release of neuropeptides and other transmitters from nerve terminals, which then activate inflammatory signaling pathways of the immune system and other tissues. C-fibers, a subpopulation of sensory neurons expressing the vanilloid-sensitive ion channel TRPV1, play a key role in the generation of neurogenic inflammation. Inflammatory sensitization of TRPV1 contributes to enhanced sensitivity to painful stimuli, known as hyperalgesia. Recent genetic and functional studies show TRPA1, another C-fiber-specific ion channel, is also substantial for full development of hyperalgesia, possibly through interaction with TRPV1. I hypothesize functional and biochemical interactions within TRP channel signaling complexes are substantial for neuronal signaling resulting in inflammatory pain and neurogenic inflammation. The aim of this project is to identify and investigate interaction partners involved in trafficking and signaling of TRPV1 and TRPA1. This project will shed new light on the intracellular molecular signaling complexes and the molecular machinery linking the receptors. My studies will provide new insights into the functional and physiological interaction of both channels and its involvement in neurogenic inflammation and thermal hyperalgesia.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Sven-Eric Jordt