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

Abstract 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.