T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity.
T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity.
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DOI：
10.1523/jneurosci.4569-09.2009
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发表时间：
2009-11-18
期刊：
影响因子：
--
通讯作者：
Fitzgerald M
中科院分区：
文献类型：
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作者：
Costigan M;Moss A;Latremoliere A;Johnston C;Verma-Gandhu M;Herbert TA;Barrett L;Brenner GJ;Vardeh D;Woolf CJ;Fitzgerald M
成年大鼠的部分周围神经损伤导致神经病理性疼痛样超敏反应，而新生大鼠则不会，这一现象也在人类中观察到。因此，我们比较了成年和新生大鼠背角的基因表达谱在周围神经病理性疼痛的备用神经损伤（SNI）模型。成年大鼠脊髓中的148个差异调节基因（而非年轻大鼠）表明，成年大鼠的小胶质细胞和T细胞反应比年轻动物更大。SNI后，T细胞在成人背角中显示大量浸润，但在新生儿中未显示。与对照组相比，T细胞缺陷型Rag 1基因缺失的成年小鼠神经性机械性异常性疼痛发生率更低，SNI后年轻和成年动物之间参与T细胞信号传导的细胞因子的中枢表达存在较大的相对差异。一种这样的细胞因子，干扰素-γ（IFNγ），在成人神经损伤后的背角上调，但不是新生儿，我们表明，IFNγ信号传导是成人神经性超敏反应的充分表达所必需的。这些数据表明，周围神经损伤后脊髓背角的T细胞浸润和活化有助于神经性疼痛样超敏反应的演变。因此，周围神经损伤后的神经免疫相互作用具有大量的适应性免疫成分，其在年轻的CNS中不存在或被抑制。
Partial peripheral nerve injury in adult rats results in neuropathic pain-like hypersensitivity, while that in neonatal rats does not, a phenomenon also observed in humans. We therefore compared gene expression profiles in the dorsal horn of adult and neonatal rats in response to the spared nerve injury (SNI) model of peripheral neuropathic pain. The 148 differentially regulated genes in adult, but not young, rat spinal cords indicate a greater microglial and T-cell response in adult than in young animals. T-cells show a large infiltration in the adult dorsal horn but not in the neonate after SNI. T-cell-deficient Rag1-null adult mice develop less neuropathic mechanical allodynia than controls, and central expression of cytokines involved in T-cell signaling exhibits large relative differences between young and adult animals after SNI. One such cytokine, interferon-γ (IFNγ), is upregulated in the dorsal horn after nerve injury in the adult but not neonate, and we show that IFNγ signaling is required for full expression of adult neuropathic hypersensitivity. These data reveal that T-cell infiltration and activation in the dorsal horn of the spinal cord following peripheral nerve injury contribute to the evolution of neuropathic pain-like hypersensitivity. The neuroimmune interaction following peripheral nerve injury has therefore a substantial adaptive immune component, which is absent or suppressed in the young CNS.