Plastic changes in sensory inputs to dorsal horn neurons following peripheral inflammation

周围炎症后背角神经元感觉输入的可塑性变化

• 批准号: 13470318
• 负责人: BABA Hiroshi
• 金额: $ 3.84万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470318/
• 关键词: Spinal dorsal horn; Hyperalgesia; Plasticity; Inflammation; Whole cell patch clamp; Prostaglandin E2; Substance-P; 膜電位画像解析; 赤外線微分干渉画像; プロスタノイド

Whole cell patch clamp recordings were made from dorsal horn neurons in thick adult rat transverse spinal cord slices with attached dorsal roots to study changes in synaptic transmission induced by peripheral inflammation and action of PGE2 on dorsal horn neurons. In naive rats, primary afferent stimulation at Aβfiber intensity elicited polysynaptic excitatory postsynaptic currents (EPSCs) in only 14 of 57 (25%) lamina II (SG) neurons. In contrast, Aβ fiber stimulation evoked polysynaptic EPSCs in 39 of 62(63%) SG neurons recorded from rats inflamed by an intraplantar injection of complete Freund's adjuvant (CFA) 48h earlier. The mean threshold intensity for eliciting EPSCs was significantly lower in cells recorded from rats with inflammation (naive : 33.2±15.1μA, n=57 ; inflamed : 22.8±11.3μA, n=62) and the mean latency of EPSCs elicited by Aβfiber stimulation in CFA-treated rats was significantly shorter than that recorded from naive rats (3.3±1.8 ms n=36 vs. 6.0±3.5 ms n=12). Bath applied PGE2 (1-20 μM) induced an inward current or membrane depolarization in the majority of deep dorsal horn neurons (laminae III-VI ; 83 of 139 cells), but only in a minority of lamina II neurons (6 of 53 cells). PGE2-induced inward currents were unaffected by perfusion with a Ca^<2+> free / high Mg^<2+> (5 mM) solution, and inhibited by flufenamic acid (50-200 μM), a nonselective cation channel blocker. The facilitation of Aβfiber-mediated input into the SG follwing peripheral inflammation may contribute to altered sensory processing. PGE2 may contribute to peripheral inflammation-induced dorsal horn neuron hyperexcitability by directly depolarizing a subset of dorsal horn neurons.

采用全细胞膜片钳记录方法，观察外周炎症对背角神经元突触传递的影响及前列腺素E_2(PGE_2)对背角神经元的作用。在幼年大鼠，Aβ纤维强度的初级传入刺激仅在57个(25%)板层(SG)神经元中诱发了多突触兴奋性突触后电流(EPSCs)。相反，刺激β纤维可在足底注射完全弗氏佐剂48h后致炎的大鼠的62个SG神经元中的39个(63%)中诱发多突触EPSCs。炎症组(33.2±15.1μA，n=5 7)和炎症组(2 2.8±11.3μA，n=62)诱发EPSCs的平均阈值强度显著降低，Aβ纤维刺激组大鼠EPSCs的平均潜伏期显著缩短(3.3±1.8ms n=36 vs.6.0±3.5ms n=12)。Bath应用前列腺素E_2(1-20μM)可引起大部分背角深部神经元(III-VI板层，139个细胞中的83个)的内向电流或膜去极化，但仅对少数II板层神经元(6/53个细胞)产生内向电流。无钙/高镁溶液(5 MM)灌流对前列腺素E_2诱发的内向电流无明显影响，但可被非选择性阳离子通道阻断剂氟芬那酸(50~200μM)抑制。Aβ纤维介导的输入促进了伴随外周炎症的SG，这可能有助于改变感觉加工。PGE2可能通过直接去极化部分背角神经元参与外周炎症诱导的背角神经元超兴奋性。

项目成果

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