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

采用膜片钳全细胞记录法，观察外周炎症诱导的突触传递变化及PGE2对脊髓背角神经元的作用。在幼稚大鼠中，a β纤维强度的初级传入刺激仅在57个II层（SG）神经元中14个（25%）中引发多突触兴奋性突触后电流（EPSCs）。相比之下，Aβ纤维刺激在48小时前足底注射完全弗氏佐剂（CFA）的大鼠中记录的62个（63%）SG神经元中的39个中诱发了多突触EPSCs。炎症大鼠的EPSCs平均阈值强度显著降低（初发：33.2±15.1μA, n=57；炎症大鼠：22.8±11.3μA, n=62）， cfa处理大鼠a β纤维刺激EPSCs的平均潜伏期显著短于初发大鼠（3.3±1.8 ms n=36 vs. 6.0±3.5 ms n=12）。PGE2 （1-20 μM）在大多数深背角神经元（III-VI层，139个细胞中的83个）中诱导向内电流或膜去极化，但仅在少数II层神经元（53个细胞中的6个）中诱导。pge2诱导的内向电流不受无Ca^<2+> /高Mg^<2+> (5 mM)溶液灌注的影响，并被氟芬那酸（50-200 μM）（一种非选择性阳离子通道阻滞剂）抑制。外周炎症后，a β纤维介导的向SG的输入可能有助于改变感觉加工。PGE2可能通过直接使一部分背角神经元去极化而参与外周炎症诱导的背角神经元高兴奋性。

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.