Dietary constituent genistein inhibits the hyperexcitability of trigeminal nociceptive neurons associated with mechanical hyperalgesia following orofacial inflammation

摘要

Objectives: Genistein, a dietary constituent, modulates voltage-dependent and ligand-gated ionic channels, suggesting that it could also attenuate inflammatory hyperalgesia. However, the mechanism underlying how genistein affects inflammation-induced hyperexcitability of nociceptive neurons in vivo remains to be determined. The present study therefore investigated whether administration of genistein could attenuate the inflammation-induced hyperexcitability of trigeminal spinal nucleus caudalis (SpVc) neurons associated with mechanical hyperalgesia in vivo. Methods: Inflammation was induced by injection of complete Freund's adjuvant into the whisker pad. The mechanical thresholds for escape behavior and electrophysiological single-unit recording of SpVc neurons responding to mechanical stimulation were then conducted in naive rats, inflamed rats, and inflamed rats with genistein administered intraperitoneally. Results: The lowered mechanical threshold in the inflamed rats was returned to control level following administration of genistein for 2 days. The mean number of discharge frequencies of SpVc neurons in inflamed rats was significantly decreased after genistein administration with both non-noxious and noxious mechanical stimuli. The increased spontaneous discharges of SpVc neurons in inflamed rats were significantly decreased after genistein administration. Noxious pinch-evoked after-discharge frequency and occurrence in inflamed rats was also significantly diminished after genistein administration, and expansion of the receptive field was significantly returned to control levels in inflamed rats. Conclusion: Herein, we present the first evidence that genistein attenuates hyperexcitability of SpVc neurons associated with inflammatory mechanical hyperalgesia. These findings suggest that genistein could be a potential therapeutic agent in complementary alternative medicine for the prevention of trigeminal inflammatory hyperalgesia.