Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.
Biochem Biophys Res Commun. 2012 May 4;421(2):318-22. doi: 10.1016/j.bbrc.2012.03.153. Epub 2012 Apr 7.
Recent observations indicate that peripheral nerve injury induces central sensitization through microglial activation and the release of inflammatory cytokines, resulting in the development of neuropathic pain. However, the underlying mechanisms of this phenomenon remain to be fully elucidated. In this study, we examined the involvement of spinal ceramide, a bioactive lipid, in the development of neuropathic pain induced by partial sciatic nerve ligation (PSL). We found that the mRNA expression levels for ceramide synthase and neutral sphingomyelinase, which are enzymes of ceramide biosynthesis, were up-regulated in the spinal cord from 3h to 1 day after PSL. The mRNA expressions of cytokines (interleukin-1β and tumor necrosis factor-α) and the microglial specific molecules (Iba-1 and CD11b) were also increased in the spinal cord after PSL. In the von Frey test, intrathecal injection of the ceramide biosynthesis inhibitors Fumonisin B1 and GW4869 at 3h and day 3 after PSL significantly attenuated PSL-induced tactile allodynia. By immunohistochemistry, microglial activation in the dorsal horn was suppressed by Fumonisin B1 and GW4869. Therefore, we conclude that spinal ceramide may play a crucial role in PSL-induced neuropathic pain through the activation of microglia.
最近的观察表明，外周神经损伤通过小胶质细胞激活和炎症细胞因子的释放诱导中枢敏化，导致神经性疼痛的发展。然而，这种现象的潜在机制仍有待充分阐明。在这项研究中，我们研究了脊髓神经酰胺（一种生物活性脂质）在部分坐骨神经结扎（PSL）诱导的神经性疼痛发展中的作用。我们发现，PSL 后 3 小时至 1 天，脊髓中神经酰胺合成酶和中性鞘磷脂酶的 mRNA 表达水平上调。PSL 后，脊髓中细胞因子（白细胞介素-1β和肿瘤坏死因子-α）和小胶质细胞特异性分子（Iba-1 和 CD11b）的 mRNA 表达也增加。在 von Frey 测试中，PSL 后 3 小时和第 3 天鞘内注射神经酰胺合成抑制剂 Fumonisin B1 和 GW4869 可显著减轻 PSL 诱导的触觉过敏。通过免疫组织化学染色，Fumonisin B1 和 GW4869 抑制了背角中小胶质细胞的激活。因此，我们得出结论，脊髓神经酰胺可能通过小胶质细胞的激活在 PSL 诱导的神经性疼痛中发挥关键作用。
