Local administration of resveratrol inhibits excitability of nociceptive wide-dynamic range neurons in rat trigeminal spinal nucleus caudalis.
Although we recently reported that intravenous administration of resveratrol suppresses trigeminal nociception, the precise peripheral effect of resveratrol on nociceptive and non-nociceptive mechanical stimulation-induced trigeminal neuron activity in vivo remains to be determined. The aim of the present study was to investigate whether local subcutaneous administration of resveratrol attenuates mechanical stimulation-induced excitability of trigeminal spinal nucleus caudalis (SpVc) neuron activity in rats, in vivo. Extracellular single-unit recordings were made of SpVc wide-dynamic range (WDR) neuron activity in response to orofacial mechanical stimulation in pentobarbital-anesthetized rats. Neurons responded to non-noxious and noxious mechanical stimulation applied to the orofacial skin. Local subcutaneous administration of resveratrol (1-10mM) into the orofacial skin dose dependently and significantly reduced the mean number of SpVc WDR neurons firing in response to both non-noxious and noxious mechanical stimuli, with the maximal inhibition of discharge frequency in response to both stimuli being seen within 5min. These inhibitory effects were no longer evident after approximately 20min. The mean magnitude of inhibition by resveratrol (10mM) of SpVc neuron discharge frequency was almost equal to that of the local anesthetic 1% lidocaine (37mM). These results suggest that local injection of resveratrol into the peripheral receptive field suppresses the excitability of SpVc neurons, possibly via inhibition of Na(+) channels in the nociceptive nerve terminals of trigeminal ganglion neurons. Therefore, local subcutaneous administration of resveratrol may provide relief of trigeminal nociceptive pain, without side effects, thus contributing to the suite of complementary and alternative medicines used as local anesthetic agents.
Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara, Kanagawa, 252-5201, Japan.
Yoshihito
Y
Shimazu
Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara, Kanagawa, 252-5201, Japan.
Eri
E
Shibuya
Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara, Kanagawa, 252-5201, Japan.
Shiori
S
Takehana
Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara, Kanagawa, 252-5201, Japan.
Kenta
K
Sekiguchi
Department of Dental Technology, The Nippon Dental University College at Tokyo, 2-3-16, Fujimi-cho, Chiyoda-ku, 102-0071, Japan.
Katsuo
K
Oshima
Department of Pediatric Dentistry, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi-cho Chiyoda-ku, Tokyo, 102-8159, Japan.
Hiroaki
H
Kamata
Department of Pediatric Dentistry, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi-cho Chiyoda-ku, Tokyo, 102-8159, Japan.
Hiroyuki
H
Karibe
Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara, Kanagawa, 252-5201, Japan. Electronic address: m-takeda@azabu-u.ac.jp.
Mamoru
M
Takeda
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008012:Lidocaine / Q000627:therapeutic use; D008297:Male; D059225:Nociception / Q000187:drug effects*; D059226:Nociceptive Pain / Q000188:drug therapy* / Q000209:etiology; D009619:Nociceptors / Q000187:drug effects*; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014279:Trigeminal Nucleus, Spinal / Q000166:cytology
D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013267:Stilbenes; D008012:Lidocaine; D000077185:Resveratrol
Complementary and alternative medicine; Extracellular single-unit recording; Lidocaine; Local anesthetic agents; Nociception; Resveratrol; Trigeminal spinal nucleus caudalis