Sulfatide‐selectin signaling in the spinal cord induces mechanical allodynia. Issue 5 (31st December 2022)

• Record Type: Journal Article
• Authors: Morita, Motoki; Watanabe, Shun; Nomura, Natsumi; Takano‐Matsuzaki, Kanako; Oyama, Misa; Iwai, Takashi; Tanabe, Mitsuo
• Is Part Of: Journal of neurochemistry. Volume 164:Issue 5(2023)
• Page Start: 658
• Page End: 670
• Publication Date: 2022-12-31
• Subjects: allodynia -- glycosphingolipid -- inflammatory pain -- selectin -- sulfatide; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.15743
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Sulfatide is a sulfated glycosphingolipid that is present abundantly in myelin sheaths of the brain and spinal cord. It is synthesized by a cerebroside sulfotransferase encoded by Gal3st1, which catalyzes the transfer of sulfate from 3′‐phosphoadenylylsulfate to galactosylceramide. We previously reported that Gal3st1 gene expression in the spinal cord is up‐regulated 1 day after intraplantar injection of complete Freund's adjuvant (CFA), indicating that sulfatide is involved in inflammatory pain. In the present study, we found that intrathecal injection of sulfatide led to mechanical allodynia. Sulfatide caused levels of glial fibrillary acidic protein (GFAP) and nitric oxide in the spinal cord to increase. Mechanical allodynia induced by intrathecal injection of sulfatide was blocked by nitric oxide synthase inhibitors and by suppression of astrocyte activation by L‐α‐aminoadipate. These results suggest that sulfatide‐induced mechanical allodynia involved glial activation and nitric oxide production. Blocking selectin, a sulfatide‐binding protein, with bimosiamose attenuated sulfatide‐induced allodynia and ameliorated CFA‐induced mechanical allodynia during inflammatory pain. Finally, elevated levels of sulfatide concentration in the spinal cord were observed during CFA‐induced inflammatory pain. The elevated sulfatide levels enhanced selectin activation in the spinal cord, resulting in mechanical allodynia. Our data suggest that sulfatide‐selectin interaction plays a key role in inflammatory pain. Abstract : Intrathecal injection of sulfatide led to mechanical allodynia. Mechanical allodynia induced by intrathecal injection of sulfatide was blocked by nitric oxide synthase inhibitors and by suppression of astrocyte activation by L‐α‐aminoadipate. Blocking selectin, a sulfatide‐binding protein, with bimosiamose attenuated sulfatide‐induced allodynia and ameliorated complete Freund's adjuvant (CFA)‐induced mechanical allodynia during inflammatory pain. Finally, elevated levels of sulfatide concentration in the spinal cord were observed during CFA‐induced inflammatory pain. The elevated sulfatide levels enhanced selectin activation in the spinal cord, resulting in mechanical allodynia. Our data suggested that sulfatide‐selectin interaction plays a key role in inflammatory pain.