Resolvin D1 suppresses inflammation-induced hyperexcitability of nociceptive trigeminal neurons associated with mechanical hyperalgesia.

Abstract

7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid (resolvin D1 [RvD1]) is biosynthesized from docosahexaenoic acid (DHA), and belongs to a novel family of lipid mediators showing remarkable anti-inflammatory effects; however, the effect of RvD1 on inflammation-induced hyperexcitability of nociceptive neurons under in vivo conditions remains to be determined. The present study, therefore, investigated whether under in vivo conditions, systemic administration of RvD1 could attenuate the inflammation-induced hyperexcitability of spinal trigeminal nucleus caudalis (SpVc) wide-dynamic range (WDR) neurons associated with hyperalgesia in rats. The threshold of escape from mechanical stimulation applied to the orofacial area in rats with complete Freund's adjuvant-induced inflammation was significantly lower than in naïve rats. The lowered mechanical threshold in rats with inflammation was returned to control levels following administration of RvD1 (3 ng/kg, i.p.) for 3 days. The mean discharge frequency of SpVc WDR neurons in rats with inflammation was significantly decreased after RvD1 administration for both non-noxious and noxious mechanical stimuli. Increased spontaneous discharge of SpVc WDR neurons in rats with inflammation was also significantly decreased after RvD1 administration. Noxious pinch-evoked afterdischarge frequency and occurrence in rats with inflammation was significantly diminished after RvD1 administration. Expansion of the receptive field in rats with inflammation also returned to control levels after RvD1 administration. These results suggest that administration of RvD1 attenuates inflammation-induced hyperexcitability of SpVc WDR neurons associated with inflammatory hyperalgesia. These findings support the idea that RvD1, derived from DHA, as well as DHA itself, are potential complementary or alternative therapeutic agents for the alleviation of inflammatory hyperalgesia.

• Authors: Anjyu Ikeda, Akari Muroki, Chie Suzuki, Yoshihito Shimazu, Mamoru Takeda
• Journal: Brain research bulletin (Brain Res Bull) Vol. 154 Pg. 61-67 (01 2020) ISSN: 1873-2747 [Electronic] United States
• PMID: 31722251 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• resolvin D1
• Docosahexaenoic Acids

Topics

• Action Potentials (drug effects)
• Animals
• Caudate Nucleus (drug effects, metabolism)
• Docosahexaenoic Acids (metabolism, pharmacology)
• Hyperalgesia (drug therapy, metabolism)
• Inflammation
• Male
• Neurons (drug effects)
• Nociceptors (drug effects, metabolism)
• Rats
• Rats, Wistar
• Trigeminal Nerve (drug effects, metabolism)
• Trigeminal Nucleus, Spinal (drug effects)