Oral nitric-oxide donor glyceryl-trinitrate induces sensitization in spinal cord pain processing in migraineurs: A double-blind, placebo-controlled, cross-over study
Corresponding Author
Armando Perrotta
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Headache Clinic, IRCCS “Neuromed”, University of Rome “Sapienza”, Pozzilli, Isernia, Italy
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Via Mondino 2, 27100 Pavia, Italy. Tel.: +39 0382 380435; fax: +39 0382 380448 [email protected].Search for more papers by this authorMariano Serrao
Neurorehabilitation Unit, University of Rome “Sapienza” Polo Pontino-ICOT, Latina, Italy
Casa di Cura Policlinico Italia, Rome, Italy
Search for more papers by this authorCristina Tassorelli
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorNatalia Arce-Leal
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorElena Guaschino
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorGrazia Sances
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorMichelangelo Bartolo
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Headache Clinic, IRCCS “Neuromed”, University of Rome “Sapienza”, Pozzilli, Isernia, Italy
Search for more papers by this authorFrancesco Pierelli
Neurorehabilitation Unit, University of Rome “Sapienza” Polo Pontino-ICOT, Latina, Italy
Search for more papers by this authorGiorgio Sandrini
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorGiuseppe Nappi
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorCorresponding Author
Armando Perrotta
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Headache Clinic, IRCCS “Neuromed”, University of Rome “Sapienza”, Pozzilli, Isernia, Italy
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Via Mondino 2, 27100 Pavia, Italy. Tel.: +39 0382 380435; fax: +39 0382 380448 [email protected].Search for more papers by this authorMariano Serrao
Neurorehabilitation Unit, University of Rome “Sapienza” Polo Pontino-ICOT, Latina, Italy
Casa di Cura Policlinico Italia, Rome, Italy
Search for more papers by this authorCristina Tassorelli
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorNatalia Arce-Leal
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorElena Guaschino
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorGrazia Sances
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorMichelangelo Bartolo
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Headache Clinic, IRCCS “Neuromed”, University of Rome “Sapienza”, Pozzilli, Isernia, Italy
Search for more papers by this authorFrancesco Pierelli
Neurorehabilitation Unit, University of Rome “Sapienza” Polo Pontino-ICOT, Latina, Italy
Search for more papers by this authorGiorgio Sandrini
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorGiuseppe Nappi
Headache Science Center, IRCCS “C. Mondino Institute of Neurology” Foundation, University of Pavia, Pavia, Italy
Search for more papers by this authorAbstract
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; 7 M; mean age 34.2±8.2) migraine and 15 (11 F; 4 M; 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.
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