The present study investigated whether daily systemic administration of docosahexaenoic acid (DHA) in rats could attenuate the hyperexcitability of trigeminal spinal nucleus caudalis (SpVc) neurons associated with hyperalgesia. Inflammation was induced in rats by injecting complete Freund's adjuvant into the whisker pads. The threshold of escape from mechanical stimulation applied to the whisker pads in inflamed rats was significantly lower than that in naïve rats. The lowered mechanical threshold in the inflamed rats was returned to that in naïve rats by 3 d intraperitoneal administration of DHA. The mean discharge frequency of SpVc neurons in inflamed rats was significantly decreased after DHA administration for 3 d with both non‐noxious and noxious mechanical stimuli. DHA administration also significantly decreased the increased spontaneous discharges of SpVc neurons in the inflamed rats, while DHA significantly diminished noxious pinch evoked after the discharge frequency and the expanded receptive field in the inflamed rats was returned to control levels. These results suggested that chronic administration of DHA attenuates inflammation‐induced mechanical hyperalgesia associated with the suppression of the hyperexcitability of SpVc neurons. These findings support the potential use of DHA as a therapeutic agent in complementary alternative medicine for mitigating trigeminal inflammatory hyperalgesia.
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