Oral nitric-oxide donor glyceryl-trinitrate induces sensitization in spinal cord pain processing in migraineurs: a double-blind, placebo-controlled, cross-over study.
Nitric-oxide donor glyceryl-trinitrate (GTN) modulates cerebral and spinal regions that are involved in migraine and pain processing. We hypothesized that in migraineurs, the susceptibility to develop a migraine attack after GTN administration should parallel with an high sensitivity to GTN-induced change in the pain processing at spinal level. We used the temporal summation threshold (TST) of the lower limb nociceptive withdrawal reflex (NWR) and the related pain sensation to study in parallel the time-course of the effect of the GTN administration on the pain processing at spinal level in migraine and healthy subjects. Twenty-eight (21 F; 7M; mean age 34.2 ± 8.2) migraine and 15 (11 F; 4M; mean age 35.9 ± 8.9) healthy subjects were recruited in a double-blind, placebo-controlled, cross-over trial. Neurophysiological examinations were carried out before (baseline) and 30', 60', 120', 180' and 240' after GTN (0.9 mg sublingual) or placebo administration during two different sessions. In migraineurs, GTN administration was associated to a significant facilitation in temporal summation of pain (reduced TST and increased painful sensation) 60', 120' and 180' after drug intake when compared to baseline, to placebo condition and to controls after GTN intake. Furthermore, in migraineurs who developed migraine after GTN, a significant facilitation in temporal summation of pain was detected 60', 120' and 180' after drug intake when compared to patients without clinical response. In migraineurs the susceptibility to develop migraine attack after GTN administration seems to be a specific trait of a subgroup of patients linked to a supersensitivity of the pain system to GTN.
Headache Science Center, IRCCS C Mondino Institute of Neurology Foundation, University of Pavia, Pavia, Italy. armando.perrotta@mondino.it
Armando
A
Perrotta
Mariano
M
Serrao
Cristina
C
Tassorelli
Natalia
N
Arce-Leal
Elena
E
Guaschino
Grazia
G
Sances
Paolo
P
Rossi
Michelangelo
M
Bartolo
Francesco
F
Pierelli
Giorgio
G
Sandrini
Giuseppe
G
Nappi
D000284:Administration, Oral; D000286:Administration, Sublingual; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D020326:Migraine without Aura / Q000188:drug therapy* / Q000503:physiopathology; D020030:Nitric Oxide Donors / Q000008:administration & dosage* / Q000009:adverse effects; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000009:adverse effects; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010919:Placebos; D011601:Psychophysics; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
D020030:Nitric Oxide Donors; D010919:Placebos; D014665:Vasodilator Agents; D005996:Nitroglycerin