Sulfatide-selectin signaling in the spinal cord induces mechanical allodynia
Sulfatide-selectin signaling in the spinal cord induces mechanical allodynia
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DOI：
10.1111/jnc.15743
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发表时间：
2022-12-31
影响因子：
4.7
通讯作者：
Tanabe，Mitsuo
中科院分区：
文献类型：
--
作者：
Morita，Motoki;Watanabe，Shun;Tanabe，Mitsuo
脑硫脂是一种硫酸化鞘糖脂，大量存在于大脑和脊髓的髓鞘中。它是由 Gal3st1 编码的脑苷脂磺基转移酶合成的，该酶催化硫酸盐从 3'-磷酸腺苷基硫酸酯转移到半乳糖苷神经酰胺。我们之前报道，足底注射完全弗氏佐剂（CFA）后1天，脊髓中的Gal3st1基因表达上调，表明脑硫脂与炎性疼痛有关。在本研究中，我们发现鞘内注射硫苷脂会导致机械性异常性疼痛。硫脂导致脊髓中胶质纤维酸性蛋白（GFAP）和一氧化氮的水平增加。一氧化氮合酶抑制剂和 L-α-氨基己二酸抑制星形胶质细胞活化可阻断鞘内注射硫脑苷脂引起的机械性异常性疼痛。这些结果表明硫脑苷脂引起的机械异常性疼痛涉及神经胶质活化和一氧化氮的产生。阻断选择素（一种硫苷脂结合蛋白），用二硫叶苷减轻硫苷脂引起的异常性疼痛，并改善炎性疼痛期间 CFA 引起的机械性异常性疼痛。最后，在 CFA 引起的炎性疼痛期间观察到脊髓中硫苷脂浓度升高。硫苷脂水平升高增强了脊髓中选择素的激活，导致机械性异常性疼痛。我们的数据表明硫苷脂-选择素相互作用在炎性疼痛中起着关键作用。
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 byGal3st1, which catalyzes the transfer of sulfate from 3′‐phosphoadenylylsulfate to galactosylceramide. We previously reported thatGal3st1gene 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.