Aspects of inflammation and nitric oxide in Cluster Headache

............................................................................................... 2 LIST OF PUBLICATIONS............................................................................ 3 ABBREVATIONS....................................................................................... 4 INTRODUCTION................................................................................................. 5 Clinical description of cluster headache................................................................5 Epidemiology.......................................................................................... 5 Genetic aspects...................................................................................... 6 Pathophysiology...................................................................................... 7 Vasodilatation....................................................................................7 Inflammation...................................................................................... 8 Hypothalamic activation.......................................................................9 Trigeminovascular system activation...................................................... 9 Autonomic nervous system imbalance..................................................10 Increase of Nitric oxide levels................................................................ 11 TREATMENT....................................................................................... 12 Acute treatment..................................................................................... 12 Prophylactic treatment............................................................................ 13 Surgical treatment................................................................................. 14 AIMS................................................................................................... 15 MATERIALS AND METHODS.................................................................. 16 Patients and Controls.............................................................................. 16 Inclusion criteria in Study I-IV............................................................. 18 CH phases studied................................................................................. 19 Methods.............................................................................................. 19 The PAXgene Blood RNA system....................................................... 19 Microarray technology...................................................................... 20 Quantitative Real-time polymerase chain reaction.................................. 22 White blood cell single photon emission computer tomography.................. 23 Capillary electrophoresis................................................................... 25 Statistics........................................................................................ 26 RESULTS............................................................................................ 28 Study I........................................................................................... 28 Study II.......................................................................................... 30 Study III......................................................................................... 31 Study IV......................................................................................... 34 DISCUSSION....................................................................................... 37 Inflammatory involvement in CH......................................................... 37 Nitric oxide in CH............................................................................. 39 Inflammation and nitric oxide – an integrated discussion........................ 41 LIMITATIONS....................................................................................... 42 CONCLUSIONS.................................................................................... 44 ACKNOWLEDGEMENTS........................................................................ 46 REFERENCES..................................................................................... 48