Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain
Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain
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DOI：
10.1523/jneurosci.0176-07.2007
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发表时间：
2007-05-30
影响因子：
5.3
通讯作者：
Ren, Ke
中科院分区：
文献类型：
--
作者：
Guo, Wei;Wang, Hu;Ren, Ke
新出现的文献暗示了胶质细胞/细胞因子在持续性疼痛中的作用。然而，这些非神经元素对中枢神经系统活动依赖性可塑性和疼痛的作用机制尚不清楚。使用三叉神经炎性痛觉过敏模型，在这里，我们提供的证据表明，胶质细胞与神经元相互作用的机制，导致活动依赖的可塑性和痛觉过敏。在咬肌炎症的反应中，在三叉神经核区域中与深口面输入的处理特别相关的胶质细胞酸性蛋白（GFAP）（星形胶质细胞的标志物）和白细胞介素-1 β（IL-1 β）（原型促炎细胞因子）上调。活化的星形胶质细胞表现出肥大和连接蛋白43（一种星形胶质细胞间隙连接蛋白）水平升高。上调的IL-1 β选择性地定位于星形胶质细胞，但不定位于小胶质细胞和神经元。咬肌神经的局部麻醉防止了炎症后GFAP和IL-1 β的增加，P物质（初级传入神经的原型神经递质）诱导了GFAP和IL-1 β的类似增加，这被一氧化氮合酶抑制剂N-G-硝基-L-精氨酸甲酯阻断。注射IL-1受体拮抗剂和神经胶质抑制剂氟柠檬酸盐可减轻炎症后的痛觉过敏和NMDA受体磷酸化。体外应用IL-1 β诱导NR 1磷酸化，其可被IL-1受体拮抗剂（PKC抑制剂）阻断（白屈菜红碱），IP 3受体抑制剂（2-氨基乙氧基二苯基硼酸盐）和磷脂酶C[1-[6-（2-氨基乙氧基二苯基硼酸盐）]抑制剂。（（17 b-3-甲氧基雌甾-1，3，5（10）-三烯-17-基）氨基）己基]-1H-吡咯-2，5-二酮]和磷脂酶A（2）（花生四烯基三氟甲基酮）。这些发现提供了组织损伤、伴随的IL-1 β诱导和通过IL-1受体信号传导的NMDA受体磷酸化偶联的星形胶质细胞活化的证据。
The emerging literature implicates a role for glia/ cytokines in persistent pain. However, the mechanisms by which these non-neural elements contribute to CNS activity-dependent plasticity and pain are unclear. Using a trigeminal model of inflammatory hyperalgesia, here we provide evidence that demonstrates a mechanism by which glia interact with neurons, leading to activity-dependent plasticity and hyperalgesia. In response to masseter inflammation, there was an upregulation of glial fibrillary acidic proteins (GFAPs), a marker of astroglia, and interleukin-1 beta(IL-1 beta), a prototype proinflammatory cytokine, in the region of the trigeminal nucleus specifically related to the processing of deep orofacial input. The activated astroglia exhibited hypertrophy and an increased level of connexin 43, an astroglial gap junction protein. The upregulated IL-1 beta was selectively localized to astrocytes but not to microglia and neurons. Local anesthesia of the masseter nerve prevented the increase in GFAP and IL-1 beta after inflammation, and substance P, a prototype neurotransmitter of primary afferents, induced similar increases in GFAP and IL-1 beta, which was blocked by a nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester. Injection of IL-1 receptor antagonist and fluorocitrate, a glial inhibitor, attenuated hyperalgesia and NMDA receptor phosphorylation after inflammation. In vitro application of IL-1 beta induced NR1 phosphorylation, which was blocked by an IL-1 receptor antagonist, a PKC inhibitor (chelerythrine), an IP3 receptor inhibitor (2-aminoethoxydiphenylborate), and inhibitors of phospholipase C[1-[6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl) amino) hexyl]-1H-pyrrole-2,5-dione] and phospholipase A(2) (arachidonyltrifluoromethyl ketone). These findings provide evidence of astroglial activation by tissue injury, concomitant IL-1 beta induction, and the coupling of NMDA receptor phosphorylation through IL-1 receptor signaling.