Balasubramanyan Sridhar, Stemkowski Patrick L, Stebbing Martin J, Smith Peter A
Department of Pharmacology and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.
J Neurophysiol. 2006 Aug;96(2):579-90. doi: 10.1152/jn.00087.2006. Epub 2006 Apr 12.
Peripheral nerve injury increases spontaneous action potential discharge in spinal dorsal horn neurons and augments their response to peripheral stimulation. This "central hypersensitivity, " which relates to the onset and persistence of neuropathic pain, reflects spontaneous activity in primary afferent fibers as well as long-term changes in the intrinsic properties of the dorsal horn (centralization). To isolate and investigate cellular mechanisms underlying "centralization," sciatic nerves of 20-day-old rats were subjected to 13-25 days of chronic constriction injury (CCI; Mosconi-Kruger polyethylene cuff model). Spinal cord slices were then acutely prepared from sham-operated or CCI animals, and whole cell recording was used to compare the properties of five types of substantia gelatinosa neuron. These were defined as tonic, irregular, phasic, transient, or delay according to their discharge pattern in response to depolarizing current. CCI did not affect resting membrane potential, rheobase, or input resistance in any neuron type but increased the amplitude and frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) in delay, transient, and irregular cells. These changes involved alterations in the action potential-independent neurotransmitter release machinery and possible increases in the postsynaptic effectiveness of glutamate. By contrast, in tonic cells, CCI reduced the amplitude and frequency of spontaneous and miniature EPSCs. Such changes may relate to the putative role of tonic cells as inhibitory GABAergic interneurons, whereas increased synaptic drive to delay cells may relate to their putative role as the excitatory output neurons of the substantia gelatinosa. Complementary changes in synaptic excitation of inhibitory and excitatory neurons may thus contribute to pain centralization.
外周神经损伤会增加脊髓背角神经元的自发放电动作电位，并增强它们对外周刺激的反应。这种与神经性疼痛的发作和持续相关的“中枢性超敏反应”，反映了初级传入纤维的自发活动以及背角内在特性的长期变化（中枢敏化）。为了分离和研究“中枢敏化”背后的细胞机制，对20日龄大鼠的坐骨神经进行了13 - 25天的慢性压迫损伤（CCI；Mosconi - Kruger聚乙烯袖套模型）。然后从假手术或CCI动物中急性制备脊髓切片，并使用全细胞记录来比较五种类型的胶状质神经元的特性。根据它们对去极化电流的放电模式，将这些神经元定义为紧张型、不规则型、相位型、瞬变型或延迟型。CCI对任何神经元类型的静息膜电位、基强度或输入电阻均无影响，但增加了延迟型、瞬变型和不规则型细胞中自发和微小兴奋性突触后电流（EPSC）的幅度和频率。这些变化涉及与动作电位无关的神经递质释放机制的改变以及谷氨酸突触后效能可能的增加。相比之下，在紧张型细胞中，CCI降低了自发和微小EPSC的幅度和频率。这种变化可能与紧张型细胞作为抑制性GABA能中间神经元的假定作用有关，而对延迟型细胞突触驱动的增加可能与它们作为胶状质兴奋性输出神经元的假定作用有关。因此，抑制性和兴奋性神经元突触兴奋的互补变化可能有助于疼痛中枢敏化。
