Docosahexaenoic acid attenuates inflammation‐induced hyperexcitability of trigeminal spinal nucleus caudalis neurons associated with hyperalgesia in rats

Abstract

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.

Phytochemical quercetin alleviates hyperexcitability of trigeminal nociceptive neurons associated with inflammatory hyperalgesia comparable to NSAIDs

“…10 We first confirmed that CFA induced hyperexcitability of SpVc WDR neurons, as described in our previous studies. [10][11][12][13] In naïve rats, spontaneous discharges were observed in 17% (1/6) of SpVc neurons (Figure 3(a) and Figure 4(c)) while most neurons fired at a low frequency with a mean firing frequency of 0.1 ± 0.2 Hz (n = 6). In contrast, all WDR neurons (6/6; 1.9 ± 0.6 Hz) were spontaneously active in inflamed rats (Figure 3(b) and Figure 4(c)).…”

Modulatory mechanism underlying how dietary constituents attenuate orofacial pain

“…The present authors recently tested the hypothesis that intraperitoneally administered dietary constituents could attenuate SpVc neuronal hypersensitivity related to mechanical hyperalgesia induced by complete Freund's adjuvant (CFA) [62,63]. In addition, the authors showed that resveratrol, DHA, and lutein provided in the diet inhibited inflammatory mechanical hyperalgesia and associated nociceptive neuronal hyperexcitability induced by CFA, possibly by inhibiting the Cox-2 converting enzyme from arachidonic acid to PGE 2 [64][65][66]. This experimental series showed (i) that the lowered escape threshold for mechanical stimulation in inflamed rats returned to control levels with ongoing administration of dietary constituents, (ii) that dietary components also reversed the high-frequency SpVc WDR discharges elicited by mechanical non-noxious and noxious stimuli, (iii) that dietary constituents returned the spontaneous discharges rates of SpVc WDR neurons as well as the noxious pinch-evoked after-discharge frequency in inflamed rats, and (iv) that control levels of receptive field expansion in inflamed rats were attained [64][65][66].…”

“…In addition, the authors showed that resveratrol, DHA, and lutein provided in the diet inhibited inflammatory mechanical hyperalgesia and associated nociceptive neuronal hyperexcitability induced by CFA, possibly by inhibiting the Cox-2 converting enzyme from arachidonic acid to PGE 2 [64][65][66]. This experimental series showed (i) that the lowered escape threshold for mechanical stimulation in inflamed rats returned to control levels with ongoing administration of dietary constituents, (ii) that dietary components also reversed the high-frequency SpVc WDR discharges elicited by mechanical non-noxious and noxious stimuli, (iii) that dietary constituents returned the spontaneous discharges rates of SpVc WDR neurons as well as the noxious pinch-evoked after-discharge frequency in inflamed rats, and (iv) that control levels of receptive field expansion in inflamed rats were attained [64][65][66]. Taken together, these findings indicate that resveratrol, lutein, and DHA significantly limited mechanical hyperalgesia induced by inflammation, probably by primary suppression of SpVc WDR neuronal hyperexcitability after attenuated peripheral COX-2 signaling (Fig.…”

“…An immunohistochemical study using a rat model of experimental tooth movement showed Cox-2 in the SpVc [73], but not in periodontal tissue, which suggests that local inhibition of Cox-2 is important in preventing and mitigating inflammatory pain associated with orthodontic tooth movement. Therefore, dietary intake of resveratrol, lutein, and DHA might attenuate mechanical hyperalgesia by inhibiting SpVc WDR excitability through the Cox-2 signaling pathway [64][65][66].…”

“…Glu, glutamate; WDR, wide dynamic range neurons. Inflammatory pain: chronic administration of the dietary constituents resveratrol, lutein, and DHA might attenuate inflammation-induced mechanical inflammatory hyperalgesia, primarily by suppressing SpVc WDR neuronal hyperexcitability via inhibition of peripheral cascades of Cox-2 signaling(64)(65)(66).…”