Department of Anesthesiology & Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
Sci Rep. 2019 Jan 29;9(1):872. doi: 10.1038/s41598-018-37318-8.
Increasing evidence indicates that pattern recognition receptors (PRRs) are involved in neuropathic pain after peripheral nerve injury (PNI). While a significant number of studies support an association between neuropathic pain and the innate immune response mediated through Toll-like receptors, a family of PRRs, the roles of other types of PRRs are largely unknown. In this study, we have focused on the macrophage-inducible C-type lectin (Mincle), a PRR allocated to the C-type lectin receptor family. Here, we show that Mincle is involved in neuropathic pain after PNI. Mincle-deficient mice showed impaired PNI-induced mechanical allodynia. After PNI, expression of Mincle mRNA was rapidly increased in the injured spinal nerve. Most Mincle-expressing cells were identified as infiltrating leucocytes, although the migration of leucocytes was also observed in Mincle-deficient mice. Furthermore, Mincle-deficiency affected the induction of genes, which are reported to contribute to neuropathic pain after PNI in the dorsal root ganglia and spinal dorsal horn. These results suggest that Mincle is involved in triggering sequential processes that lead to the pathogenesis of neuropathic pain.
越来越多的证据表明,模式识别受体(PRRs)参与外周神经损伤(PNI)后的神经病理性疼痛。虽然大量研究支持神经病理性疼痛与 Toll 样受体(TLRs)介导的先天免疫反应之间存在关联,TLRs 是 PRR 家族的一种,但其他类型 PRR 的作用在很大程度上尚不清楚。在这项研究中,我们专注于巨噬细胞诱导的 C 型凝集素(Mincle),一种分配到 C 型凝集素受体家族的 PRR。在这里,我们表明 Mincle 参与 PNI 后的神经病理性疼痛。Mincle 缺陷型小鼠表现出机械性痛觉过敏的损伤诱导受损。在 PNI 后,损伤的脊神经中 Mincle mRNA 的表达迅速增加。大多数表达 Mincle 的细胞被鉴定为浸润白细胞,尽管在 Mincle 缺陷型小鼠中也观察到白细胞的迁移。此外,Mincle 缺陷型影响报告在背根神经节和脊髓背角中有助于 PNI 后神经病理性疼痛的基因的诱导。这些结果表明 Mincle 参与触发导致神经病理性疼痛发病机制的连续过程。