Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, Adelaide 5005, Australia.
Brain Behav Immun. 2011 Mar;25(3):503-13. doi: 10.1016/j.bbi.2010.11.018. Epub 2010 Dec 4.
Recent evidence demonstrates that peripheral immune cells contribute to the nociceptive hypersensitivity associated with neuropathic pain by infiltrating the central nervous system (CNS). We have recently developed a rat model of graded chronic constriction injury (CCI) by varying the exposure of the sciatic nerve and control non-nerve tissue to surgical placement of chromic gut. We demonstrate that splenocytes can contribute significantly to CCI-induced allodynia, as adoptive transfer of these cells from high pain donors to low pain recipients potentiates allodynia (P<0.001). The phenomenon was replicated with peripheral blood mononuclear cells (P<0.001). Adoptive transfer of allodynia was not achieved in sham recipients, indicating that peripheral immune cells are only capable of potentiating existing allodynia, rather than establishing allodynia. As adoptively transferred cells were found by flow cytometry to migrate to the spleen (P<0.05) and potentiation of allodynia was prevented in splenectomised low pain recipients, adoptive transfer of high pain splenocytes may induce the migration of host-derived immune cells from the spleen to the CNS as observed by flow cytometry (P<0.05). Importantly, intrathecal transfer of CD45(+) cells prepared from spinal cords of high pain donors into low pain recipients led to potentiated allodynia (P<0.001), confirming that infiltrating immune cells are not passive bystanders, but actively contribute to nociceptive hypersensitivity in the lumbar spinal cord.
最近的证据表明，外周免疫细胞通过浸润中枢神经系统（CNS），导致与神经病理性疼痛相关的痛觉过敏。我们最近通过改变坐骨神经和对照非神经组织暴露于铬肠线的手术位置，开发了一种分级慢性缩窄性损伤（CCI）的大鼠模型。我们证明脾细胞可以显著促进CCI 诱导的痛觉过敏，因为将这些细胞从高痛供体过继转移到低痛受体中可以增强痛觉过敏（P<0.001）。外周血单核细胞（P<0.001）也复制了这种现象。在假手术受体中未实现痛觉过敏的过继转移，表明外周免疫细胞只能增强现有的痛觉过敏，而不能建立痛觉过敏。通过流式细胞术发现过继转移的细胞迁移到脾脏（P<0.05），并且在脾切除的低痛受体中，痛觉过敏的增强被阻止，因此高痛脾细胞的过继转移可能诱导源自宿主的免疫细胞从脾脏迁移到中枢神经系统，如流式细胞术观察到的那样（P<0.05）。重要的是，将高痛供体脊髓中制备的 CD45(+)细胞鞘内转移到低痛受体中，导致痛觉过敏增强（P<0.001），证实浸润的免疫细胞不是被动旁观者，而是积极参与腰椎脊髓中的伤害感受性过敏。
