title: Nitroglycerin sensitises in healthy subjects CNS structures involved in migraine pathophysiology: evidence from a study of nociceptive blink reflexes and visual evoked potentials.
abstract: Nitroglycerin (NTG), a NO donor, induces an attack in migraine patients approximately 4-6 h after administration. The causative mechanisms are not known, but the long delay leaves room for a central effect, such as a change in neuronal excitability and synaptic transmission of various CNS areas involved in pain and behaviour including trigeminal nucleus caudalis and monoaminergic brain stem nuclei. To explore the central action of NTG, we have studied its effects on amplitude and habituation of the nociceptive blink reflex (nBR) and the visual evoked potential (VEP) before, 1 h and 4 h after administration of NTG (1.2 mg sublingual) or placebo (vehicle sublingual) in two groups of 10 healthy volunteers. We found a significant decrease in nBR pain and reflex thresholds both 1 and 4 h post-NTG. At the 4 h time point R2 latency was shorter (p=0.04) and R2 response area increased (p<0.01) after NTG but not after placebo. Habituation tended to become more pronounced after both NTG and placebo administration. There was a significant amplitude increase in the 5th VEP block (p=0.03) at 1h after NTG and in the 1st block (p=0.04) at 4 h. VEP habituation was replaced by potentiation at both delays after NTG; the change in habituation slope was significant at 1h (p=0.02). There were no significant VEP changes in subjects who received sublingual placebo. In conclusion, we found that in healthy subjects sublingual NTG, but not its vehicle, induces changes in a trigeminal nociceptive reflex and an evoked cortical response which are comparable to those found immediately before and during an attack of migraine. These changes could be relevant for the attack-triggering effect of NTG in migraineurs.
authors.affiliation: Headache Research Unit, Department of Neurology, University of Liège, CHR Citadelle, Bld. du 12ème de Ligne 1, B-4000 Liège, Belgium.
authors.forename: Laura
authors.initials: L
authors.lastname: Di Clemente
authors.forename: Gianluca
authors.initials: G
authors.lastname: Coppola
authors.forename: Delphine
authors.initials: D
authors.lastname: Magis
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Gérardy
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fumal
authors.forename: Victor
authors.initials: V
authors.lastname: De Pasqua
authors.forename: Vittorio
authors.initials: V
authors.lastname: Di Piero
authors.forename: Jean
authors.initials: J
authors.lastname: Schoenen
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001767:Blinking / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography / Q000379:methods; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D005260:Female; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced* / Q000503:physiopathology*; D020030:Nitric Oxide Donors / Q000009:adverse effects* / Q000494:pharmacology; D005996:Nitroglycerin / Q000009:adverse effects* / Q000494:pharmacology; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D055815:Young Adult
chemical_list: D020030:Nitric Oxide Donors; D005996:Nitroglycerin