title: Phosphodiesterases 3 and 5 express activity in the trigeminal ganglion and co-localize with calcitonin gene-related peptide.
abstract: BACKGROUND
  Understanding of the neuropathology leading to migraine pain has centered on either a vascular or neuronal origin. Sildenafil, a specific inhibitor of phosphodiesterase 5 (PDE5), induces migraine-like headache in a human headache model without concomitant artery dilation. The presence and activity of PDE3 and PDE5 is known in cerebral arteries. However, the presence in the neuronal part of the trigeminovascular pathway, i.e. the trigeminal ganglion and the possible co-localization with calcitonin gene-related peptide (CGRP), is not known.
  
  
  METHODS
  Rat trigeminal ganglia were isolated and immunohistochemistry and in situ hybridization was applied. Evaluations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) hydrolysis were performed using scintillation proximity assays.
  
  
  RESULTS
  PDE3 and PDE5 were present and active in the trigeminal ganglia. A subset of PDE3- and PDE5-positive neurons contained CGRP. In contrast to cGMP, both sildenafil and cilostazol influenced cAMP hydrolysis.
  
  
  CONCLUSIONS
  Sildenafil may exert its effect on the neuronal part of the migraine pain pathway. In addition to the effects on cGMP signaling, sildenafil may indirectly affect cAMP signaling in the trigeminal ganglion. This result may suggest a common cAMP-related pathway for sildenafil, cilostazol, and CGRP in eliciting migraine pain.
authors: Lundbeck Foundation Center for Neurovascular signaling (LUCENS), Glostrup Research Institute, University of Copenhagen, Glostrup Hospital, Denmark.
authors: Julie C
authors: JC
authors: Nordgaard
authors: Department of Clinical Experimental Research, Glostrup Hospital, University of Copenhagen, Denmark.
authors: Lars S
authors: LS
authors: Kruse
authors: Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors: Morten
authors: M
authors: Møller
authors: Lundbeck Foundation Center for Neurovascular signaling (LUCENS), Glostrup Research Institute, University of Copenhagen, Glostrup Hospital, Denmark Department of Neurology, Herlev University Hospital, Denmark ckruuse@dadlnet.dk.
authors: Christina
authors: C
authors: Kruuse
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D008881:Migraine Disorders / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000378:metabolism* / Q000473:pathology*
chemical_list: D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D015740:Calcitonin Gene-Related Peptide
keywords: Trigeminal ganglion; calcitonin gene-related peptide; migraine; phosphodiesterase 3; phosphodiesterase 5