ArticlesNitroglycerin sensitises in healthy subjects CNS structures involved in migraine pathophysiology: Evidence from a study of nociceptive blink reflexes and visual evoked potentialsDi Clemente, Lauraa,b; Coppola, Gianlucac; Magis, Delphinea; Gérardy, Pierre-Yvesa; Fumal, Arnauda; De Pasqua, Victora; Di Piero, Vittoriob; Schoenen, Jeana,*Author Information aHeadache Research Unit, Department of Neurology, University of Liège, CHR Citadelle, Bld. du 12ème de Ligne 1, B – 4000 Liège, Belgium bDepartment of Neurological Sciences, University “La Sapienza”, Rome, Italy cDepartment of Neurophysiology of Vision and Neuro-ophthalmology, G.B. Bietti Eye Foundation-IRCCS, Rome, Italy *Corresponding author. Tel.: +32 4 225 63 91; fax: +32 4 225 64 51. E-mail address:[email protected] ARTICLE INFO Article history: Received July 24, 2008 Received in revised form March 1, 2009 Accepted April 8, 2009. Pain: July 2009 - Volume 144 - Issue 1 - p 156-161 doi: 10.1016/j.pain.2009.04.018 Buy Metrics 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 1 h 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 1 h (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. © 2009 Lippincott Williams & Wilkins, Inc.