title: Resveratrol attenuates inflammation-induced hyperexcitability of trigeminal spinal nucleus caudalis neurons associated with hyperalgesia in rats.
abstract: BACKGROUND
  Resveratrol, a component of red wine, has been reported to decrease prostaglandin E2 production by inhibiting the cyclooxygenase-2 cascade and to modulate various voltage-dependent ion channels, suggesting that resveratrol could attenuate inflammatory hyperalgesia. However, the effects of resveratrol on inflammation-induced hyperexcitability of nociceptive neurons in vivo remain to be determined. Thus, the aim of the present study was to determine whether daily systemic administration of resveratrol to rats attenuates the inflammation-induced hyperexcitability of spinal trigeminal nucleus caudalis wide-dynamic range neurons associated with hyperalgesia.
  
  
  RESULTS
  Inflammation was induced by injection of complete Freund's adjuvant into the whisker pad. The threshold of escape from mechanical stimulation applied to whisker pad in inflamed rats was significantly lower than in control rats. The decreased mechanical threshold in inflamed rats was restored to control levels by daily systemic administration of resveratrol (2 mg/kg, i.p.). The mean discharge frequency of spinal trigeminal nucleus caudalis wide-dynamic range neurons to both nonnoxious and noxious mechanical stimuli in inflamed rats was significantly decreased after resveratrol administration. In addition, the increased mean spontaneous discharge of spinal trigeminal nucleus caudalis wide-dynamic range neurons in inflamed rats was significantly decreased after resveratrol administration. Similarly, resveratrol significantly diminished noxious pinch-evoked mean after discharge frequency and occurrence in inflamed rats. Finally, resveratrol restored the expanded mean size of the receptive field in inflamed rats to control levels.
  
  
  CONCLUSIONS
  These results suggest that chronic administration of resveratrol attenuates inflammation-induced mechanical inflammatory hyperalgesia and that this effect is due primarily to the suppression of spinal trigeminal nucleus caudalis wide dynamic range neuron hyperexcitability via inhibition of both peripheral and central cyclooxygenase-2 cascade signaling pathways. These findings support the idea of resveratrol as a potential complementary and alternative medicine for the treatment of trigeminal inflammatory hyperalgesia without side effects.
authors.affiliation: Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Sekiguchi
authors.affiliation: Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Takehana
authors.affiliation: Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Shibuya
authors.affiliation: Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Nichiwa
authors.initials: N
authors.lastname: Matsuzawa
authors.affiliation: Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Hidaka
authors.affiliation: Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Yurie
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Laboratory of Physiology II, Department of Veterinary Science, School of Veterinary medicine, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Inoue
authors.affiliation: FANCL Health Science Research Center, Research Institute, FANCL Corporation, Yokohama, Kanagawa, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Shimazu
authors.affiliation: Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Sagamihara, Kanagawa, Japan m-takeda@azabu-u.ac.jp.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Takeda
mesh_terms: D000818:Animals; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology*; D007249:Inflammation / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects / Q000473:pathology*
chemical_list: D013267:Stilbenes; D000077185:Resveratrol
keywords: Inflammation; cyclooxygenase; hyperalgesia; resveratrol; single unit recording; trigeminal system