6. Glutamate Receptor Ionotropic AMPA 3 (GRIA3) gene polymorphism influences cortical response to somatosensory stimulation in medication-overuse headache patients

Abstract

Glutamate-mediated pathways seem to play a relevant role in the generation of somatosensory evoked potentials (SSEPs) in supragranular parietal layers, but also in maintaining central sensitization, a mechanism that may be responsible for medication overuse headache (MOH). Here, we tested whether Glutamate Receptor Ionotropic AMPA 3 (GRIA3) rs3761555 polymorphisms may influence SSEPs sensitization and habituation in patients with MOH. We recorded median nerve SSEPs (two blocks of 100 sweeps) in 60 MOH patients. We measured N20-P25 1st block amplitude, as a marker of sensitization, and amplitude changes between two sequential blocks, as a marker of habituation. According to their genotype, patients were divided in three groups: “T/T” (N = 27), “T/C” (N = 26) and “C/C” (N = 7). No differences emerged among genotypes in terms of grand-average for all the neurophysiological measures. Patients carrying T/T polymorphism had larger-amplitude block 1 SSEP than those carrying C/C (z = 2.604; p = 0.028), with T/C falling in between. No between groups differences were observed regarding delayed habituation. In patients with MOH, GRIA3 rs3761555 polymorphisms influence SSEP sensitization and, in general, cortical excitability. These data suggest that the glutamatergic system is one of the main drivers of central sensitization in MOH patients.