The bilateral change of the spinal cord and dorsal root ganglion glycosyltransferase expression involved in glycosphingolipids biosynthesis during inflammatory pain

[Speaker] Motoki Morita:1,2
[Co-author] Shun Watanabe:1,2, Natsumi Nomura:1,2, Misa Oyama:1,2, Takashi Iwai:1,2, Mitsuo Tanabe:1,2
1:Laboratory of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Japan, 2:Medicinal Research Laboratories, School of Pharmacy, Kitasato University, Japan

Sialyl glycosphingolipids are abundant in the nerve system and play physiological roles such as axon-myelin interaction, axonal elongation and maintenance. The glycosphingolipids are divided into glucosylceramide-based glycosphingolipids or galactosylceramide-based glycosphingolipids, depending on the biosynthetic pathway. Glucosylceramides, the starting material for biosynthesis of almost glycosphingolipids, are synthesized from ceramide and UDP-glucose. Gangliosides are synthesized by additional carbohydrates thereafter. On the other hand, sulfatide, the major lipid component of myelin, is synthesized from galactosylceramide. Our previous study revealed that intraplantar injection of b-series gangliosides caused hyperalgesia and mechanical allodynia. In this study, we investigated whether complete Freund's adjuvant (CFA)-induced inflammatory pain affected the gene expression involved in glycosphingolipids synthesis. After unilateral intraplantar CFA injection into ICR male mice, mechanical allodynia was assessed at several time points using von Frey filaments. We detected mirror image pain which was characterized by mechanical hypersensitivity on the uninjured side during chronic inflammatory pain stage (15 days after CFA injection); that is, mechanical allodynia was caused in not only the inflamed paw but also the non-inflamed paw 15 days after CFA injection. In this stage and acute (1 day after CFA injection) inflammatory stage, we measured the glycosyltransferase gene expression in both the inflammatory and non-inflammatory side.
To measure the differences in the expression of glycosyltransferases, qRT-PCR were used for analysis of mRNA amounts in the spinal cord and dorsal root ganglion (DRG). The expression patterns of glycosyltransferases were dependent on the tissues and inflammatory stages. Several glycosyltransferases were upregulated during acute inflammatory pain in both DRG and spinal cords. On the other hand, we found the downregulation of almost glycosyltransferases in the spinal cord during the chronic stage. In addition, the glycosyltransferase expression patterns were similar bilaterally, suggesting that the change of glycosyltransferase expression patterns were associated with mirror image pain. Future studies were required to reveal the molecular mechanisms how the glycosphingolipids are involved in inflammatory pain and mirror image pain.

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