Intracellular transduction mechanisms in migraine

Members
Christina Kruuse, Carina Jørgensen, Lars Schack Kruse, Julie Carøe Kristensen.

Background
In order to fully understand the cellular signalling behind the effects of headache inducing substances in humans, basic molecular studies are warranted applying the compounds in isolated tissue or cells to supplement the results from modulating specific signalling pathways in human. Pain signalling in humans involve second messenger signalling through second messengers; cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). We know from human studies that specific modulation of such signalling by inhibiting the breakdown of cyclic nucleotides induce headache, though the tissues in which the processes take place not the possible interaction is not fully understood. We aim to localize and investigate the role of cyclic nucleotide signalling in tissue and cells relevant for the pain process. In collaboration with Department of Clinical Biochemistry Glostrup, Department of Neuroscience and Pharmacology and Functional Imaging Unit and Dept Clinical Physiology and Nuclear medicine we have found unique localisation and function of molecules, phosphodiesterases (PDE), responsible for modulation of cGMP and cAMP signalling in cerebral arteries and the brain.

Current projects
We have described the unique presence of specific PDEs in the cerebral arteries and trigeminovascular system, and is currently investigating the co-localisation of PDEs with other relevant cellular signalling molecules in vascular and neuronal cell systems. Further, by modulation of the cells and tissue with inhibitors of specific PDEs as well as migraine related substances, we try to locate potential new targets for treatment in the pain mechanism of headache and migraine.

Collaboration
Henrik Larsson and Adam Espe Hansen (Functional Imaging Unit, Department of Clinical Physiology); Morten Møller (Department of Neurobiology and Pharmacology, Panum Institute); Andreas Straube (Dept Neurology, Clinicum Grosshardern, Munich, Germany); Joe Beavo and Sergei Rybalkin (Dept Pharmacology, University of Washington, Seattle); Lars Edvinsson (Department of Experimental Clinical Research, Glostrup Hospital); Steen Gammeltoft (Dept. Clinical Biochemistry, Glostrup).