Effect of theanine on the hyperexcitability of trigeminal secondary nociceptive neurons following orofacial inflammation in rats.

The present in vivo study investigated whether systemic administration of theanine attenuates the inflammation-induced hyperexcitability of trigeminal spinal nucleus caudalis (SpVc) neurons associated with hyperalgesia. Complete Freund's adjuvant (CFA) was injected into the whisker pads of 24 rats to induce inflammation, and then mechanical stimulation was applied to the orofacial area to assess the threshold of escape. The mechanical threshold was statistically significantly lower in CFA-inflamed rats compared to uninjected naïve rats, and this lowered threshold returned to control levels after 2 days of theanine administration. The mean discharge frequency of SpVc wide-dynamic range (WDR) neurons to mechanical stimuli in anesthetized CFA-inflamed rats was statistically significantly lower after two days of theanine administration. In addition, the increased mean spontaneous discharge of SpVc WDR neurons in CFA-inflamed rats statistically significantly decreased after theanine administration. Similarly, theanine restored the expanded mean receptive field size in CFA-inflamed rats to control levels. Taken together, these results suggest that administration of theanine attenuates inflammatory hyperalgesia associated with hyperexcitability of nociceptive SpVc WDR neurons. These findings support the potential of theanine as a therapeutic agent in complementary alternative medicine strategies to prevent inflammatory hyperalgesia.

Local Administration of the Phytochemical, Quercetin, Attenuates the Hyperexcitability of Rat Nociceptive Primary Sensory Neurons Following Inflammation Comparable to lidocaine.

Although in vivo local injection of quercetin into the peripheral receptive field suppresses the excitability of rat nociceptive trigeminal ganglion (TG) neurons, under inflammatory conditions, the acute effects of quercetin in vivo, particularly on nociceptive TG neurons, remain to be determined. The aim of this study was to examine whether acute local administration of quercetin into inflamed tissue attenuates the excitability of nociceptive TG neurons in response to mechanical stimulation. The mechanical escape threshold was significantly lower in complete Freund's adjuvant (CFA)-inflamed rats compared to before CFA injection. Extracellular single-unit recordings were made from TG neurons of CFA-induced inflammation in anesthetized rats in response to orofacial mechanical stimulation. The mean firing frequency of TG neurons in response to both non-noxious and noxious mechanical stimuli was reversibly inhibited by quercetin in a dose-dependent manner (1-10 mM). The mean firing frequency of inflamed TG neurons in response to mechanical stimuli was reversibly inhibited by the local anesthetic, 1% lidocaine (37 mM). The mean magnitude of inhibition on TG neuronal discharge frequency with 1 mM quercetin was significantly greater than that of 1% lidocaine. These results suggest that local injection of quercetin into inflamed tissue suppresses the excitability of nociceptive primary sensory TG neurons. PERSPECTIVE: Local administration of the phytochemical, quercetin, into inflamed tissues is a more potent local analgesic than voltage-gated sodium channel blockers as it inhibits the generation of both generator potentials and action potentials in nociceptive primary nerve terminals. As such, it contributes to the area of complementary and alternative medicines.

Suppression of the excitability of rat nociceptive secondary sensory neurons following local administration of the Phytochemical, (-)-Epigallocatechin-3-gallate.

The phytochemical, polyphenolic compound, (-)-epigallocatechin-3-gallate (EGCG), is the main catechin found in green tea. Although a modulatory effect of EGCG on voltage-gated sodium and potassium channels has been reported in excitable tissues, the in vivo effect of EGCG on the excitability of nociceptive sensory neurons remains to be determined. Our aim was to investigate whether local administration of EGCG to rats attenuates the excitability of nociceptive spinal trigeminal nucleus caudalis (SpVc) neurons in response to mechanical stimulation in vivo. Extracellular single unit recordings were made from SpVc neurons in response to orofacial mechanical stimulation of anesthetized rats. The mean firing frequency of SpVc wide-dynamic range neurons following both non-noxious and noxious mechanical stimuli was significantly inhibited by EGCG in a dose-dependent and reversible manner. The mean magnitude of inhibition by EGCG on SpVc neuronal discharge frequency was similar to that of the local anesthetic, 1% lidocaine. Local injection of half-dose of lidocaine replaced the half-dose of EGCG. These results suggest that local injection of EGCG suppresses the excitability of nociceptive SpVc neurons, possibly via the inhibition of voltage-gated sodium channels and opening of voltage-gated potassium channels in the trigeminal ganglion. Therefore, administration of EGCG as a local anesthetic may provide relief from trigeminal nociceptive pain without side effects.

Suppression of the Excitability of Rat Nociceptive Primary Sensory Neurons Following Local Administration of the Phytochemical, Quercetin.

Although the modulatory effect of quercetin on voltage-gated Na, K, and Ca channels has been studied in vitro, the in vivo effect of quercetin on the excitability of nociceptive primary neurons remains to be determined. The aim of the present study was to examine whether acute local quercetin administration to rats attenuates the excitability of nociceptive trigeminal ganglion (TG) neurons in response to mechanical stimulation in vivo. Extracellular single unit recordings were made from TG neurons of anesthetized rats in response to orofacial non-noxious and noxious mechanical stimulation. The mean firing frequency of TG neurons in response to both non-noxious and noxious mechanical stimuli was dose-dependently inhibited by quercetin, and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 10 min. The inhibitory effect of quercetin lasted for 15 minutes and was reversible. The mean magnitude of inhibition on TG neuronal discharge frequency with 10 mM quercetin was almost equal to that of the local anesthetic, 2% lidocaine. These results suggest that local injection of quercetin into the peripheral receptive field suppresses the excitability of nociceptive primary sensory neurons in the TG, possibly via inhibition of voltage-gated Na channels and opening voltage-gated K channels. PERSPECTIVE: Local administration of the phytochemical, quercetin, as a local anesthetic may provide relief from trigeminal nociceptive pain with smallest side effects, thus contributing to the area of complementary and alternative medicines.