The dietary constituent resveratrol suppresses nociceptive neurotransmission via the NMDA receptor.
Background Although we have previously reported that intravenous resveratrol administration inhibits the nociceptive neuronal activity of spinal trigeminal nucleus caudalis neurons, the site of the central effect remains unclear. The aim of the present study was to examine whether acute intravenous resveratrol administration in the rat attenuates central glutamatergic transmission of spinal trigeminal nucleus caudalis neurons responding to nociceptive mechanical stimulation in vivo, using extracellular single-unit recordings and microiontophoretic techniques. Results Extracellular single-unit recordings using multibarrel electrodes were made from the spinal trigeminal nucleus caudalis wide dynamic range neurons responding to orofacial mechanical stimulation in pentobarbital anesthetized rats. These neurons also responded to iontophoretic application of glutamate, and the evoked neuronal discharge frequency was significantly increased in a current-dependent and reversible manner. The mean firing frequency evoked by the iontophoretic application of glutamate (30, 50, and 70 nA) was mimicked by the application of 10 g, 60 g, and noxious pinch mechanical stimulation, respectively. The mean firing frequency of spinal trigeminal nucleus caudalis wide dynamic range neurons responding to iontophoretic application of glutamate and N-methyl-D-aspartate were also significantly inhibited by intravenous administration of resveratrol (2 mg/kg) and the maximal inhibition of discharge frequency was observed within 10 min. These inhibitory effects lasted approximately 20 min. The relative magnitude of inhibition by resveratrol of the glutamate-evoked spinal trigeminal nucleus caudalis wide dynamic range neuronal discharge frequency was similar to that for N-methyl-D-aspartate iontophoretic application. Conclusion These results suggest that resveratrol suppresses glutamatergic neurotransmission of the spinal trigeminal nucleus caudalis neurons responding to nociceptive mechanical stimulation via the N-methyl-D-aspartate receptor in vivo, and resveratrol may be useful as a complementary or alternative therapeutic agent for the treatment of trigeminal nociceptive pain.
1 Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Kanagawa, Japan.
Shiori
S
Takehana
2 FANCL Health Science Research Center, Research Institute, FANCL Corporation, Kanagawa, Japan.
Yoshiko
Y
Kubota
2 FANCL Health Science Research Center, Research Institute, FANCL Corporation, Kanagawa, Japan.
Nobuo
N
Uotsu
2 FANCL Health Science Research Center, Research Institute, FANCL Corporation, Kanagawa, Japan.
Kei
K
Yui
3 Department of Physiology, School of Dentistry, Nihon University, Tokyo, Japan.
Koichi
K
Iwata
1 Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Kanagawa, Japan.
Yoshihito
Y
Shimazu
1 Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Kanagawa, Japan.
Mamoru
M
Takeda
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy*; D007478:Iontophoresis; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D000077185:Resveratrol; D011984:Sensory Receptor Cells / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D014279:Trigeminal Nucleus, Spinal / Q000166:cytology*
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D013267:Stilbenes; D018698:Glutamic Acid; D016202:N-Methylaspartate; D000077185:Resveratrol
Iontophoretic application; alternative medicine; resveratrol; single-unit recording; trigeminal spinal nucleus caudalis