Investigations into migraine pathogenesis: time course for effects of m-CPP, BW723C86 or glyceryl trinitrate on appearance of Fos-like immunoreactivity in rat trigeminal nucleus caudalis (TNC).
Clinical and preclinical studies suggest that 5-HT and nitric oxide (NO) mobilization within the trigeminovascular system is fundamental to the initiation of migraine attacks., e.g. m-chlorophenylpiperazine (m-CPP) and glyceryl trinitrate (GTN) induce headache in humans. 5-HT2B receptors are known to mediate NO-dependent vasorelaxation in peripheral blood vessels, raising the possibility that this receptor is implicated in the pathogenesis of the disease. Therefore, we measured the effects of 5-HT2B agonists (m-CPP or BW723C86) or GTN on trigeminal nerves by quantifying Fos expression in the rat TNC. m-CPP (0.1 mg/kg, i.v.) induced time-dependent elevations in Fos-LI in the rat TNC 2 h and 8 h after injection. In contrast, neither intravenous GTN (0.5 microg/kg per min, infused 20 min) nor BW723C86 (0.1 mg/kg, i.v.) increased Fos-LI at 2 h or 8 h after administration. These data are not consistent with the involvement of the 5-HT2B/2C receptors or NO in trigeminovascular activation, and by inference migraine, and suggest the contribution of some other unidentified pathway.
Martin
R S
RS
Neurobiology Unit, Roche Bioscience, Palo Alto, CA 94304, USA. renee.martin@roche.com
Martin
G R
GR
D000818:Animals; D016762:Genes, fos / Q000276:immunology* / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology*; D008881:Migraine Disorders / Q000209:etiology* / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors; D014275:Trigeminal Caudal Nucleus / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000494:pharmacology*
C092430:1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; D007211:Indoles; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D013876:Thiophenes; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin; C015068:1-(3-chlorophenyl)piperazine