Hogan Q H, McCallum J B, Sarantopoulos C, Aason M, Mynlieff M, Kwok W M, Bosnjak Z J
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Pain. 2000 May;86(1-2):43-53. doi: 10.1016/s0304-3959(99)00313-9.
Hyperexcitability of the primary afferent neuron leads to neuropathic pain following injury to peripheral axons. Changes in calcium channel function of sensory neurons following injury have not been directly examined at the channel level, even though calcium is a primary second messenger-regulating neuronal function. We compared calcium currents (I(Ca)) in 101 acutely isolated dorsal root ganglion neurons from 31 rats with neuropathic pain following chronic constriction injury (CCI) of the sciatic nerve, to cells from 25 rats with normal sensory function following sham surgery. Cells projecting to the sciatic nerve were identified with a fluorescent label applied at the CCI site. Membrane function was determined using patch-clamp techniques in current clamp mode, and in voltage-clamp mode using solutions and conditions designed to isolate I(Ca). Somata of peripheral sensory neurons from hyperalgesic rats demonstrated decreased I(Ca). Peak calcium channel current density was diminished by injury from 3.06+/-0.30 pS/pF to 2. 22+/-0.26 pS/pF in medium neurons, and from 3.93+/-0.38 pS/pF to 2. 99+/-0.40 pS/pF in large neurons. Under these voltage and pharmacologic conditions, medium-sized neuropathic cells lacked obvious T-type calcium currents which were present in 25% of medium-sized cells from control animals. Altered Ca(2+) signalling in injured sensory neurons may contribute to hyperexcitability leading to neuropathic pain.
外周轴突损伤后，初级传入神经元的兴奋性过高会导致神经性疼痛。尽管钙是调节神经元功能的主要第二信使，但损伤后感觉神经元钙通道功能的变化尚未在通道水平上进行直接检测。我们将31只坐骨神经慢性压迫损伤（CCI）后出现神经性疼痛的大鼠的101个急性分离背根神经节神经元中的钙电流（I(Ca)），与25只假手术后具有正常感觉功能的大鼠的细胞进行了比较。通过在CCI部位施加荧光标记来识别投射到坐骨神经的细胞。使用膜片钳技术在电流钳模式下测定膜功能，并在电压钳模式下使用旨在分离I(Ca)的溶液和条件进行测定。来自痛觉过敏大鼠的外周感觉神经元的胞体表现出I(Ca)降低。在中型神经元中，钙通道电流峰值密度因损伤从3.06±0.30 pS/pF降至2.22±0.26 pS/pF，在大型神经元中从3.93±0.38 pS/pF降至2.99±0.40 pS/pF。在这些电压和药理学条件下，中型神经性细胞缺乏明显的T型钙电流，而对照动物的中型细胞中有25%存在这种电流。损伤的感觉神经元中Ca(2+)信号的改变可能导致兴奋性过高，进而引发神经性疼痛。
