Yang Fei, Zhang Chen, Xu Qian, Tiwari Vinod, He Shao-Qiu, Wang Yun, Dong Xinzhong, Vera-Portocarrero Louis P, Wacnik Paul W, Raja Srinivasa N, Guan Yun
Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Neuromodulation. 2015 Jan;18(1):33-40; discussion 40. doi: 10.1111/ner.12249. Epub 2014 Oct 10.
Recent clinical studies suggest that neurostimulation at the dorsal root entry zone (DREZ) may alleviate neuropathic pain. However, the mechanisms of action for this therapeutic effect are unclear. Here, we examined whether DREZ stimulation inhibits spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats.
We conducted in vivo extracellular single-unit recordings of WDR neurons in rats after an L5 spinal nerve ligation (SNL) or sham surgery. We set bipolar electrical stimulation (50 Hz, 0.2 msec, 5 min) of the DREZ at the intensity that activated only Aα/β-fibers by measuring the lowest current at which DREZ stimulation evoked a peak antidromic sciatic Aα/β-compound action potential without inducing an Aδ/C-compound action potential (i.e., Ab1).
The elevated spontaneous activity rate of WDR neurons in SNL rats (n = 25; data combined from post-SNL groups at days 14-16 [n = 15] and days 45-75 [n = 10]) was significantly decreased from the prestimulation level (p < 0.01) at 0-15 min and 30-45 min post-stimulation. In both sham-operated (n = 8) and nerve-injured rats, DREZ stimulation attenuated the C-component, but not the A-component, of the WDR neuronal response to graded intracutaneous electrical stimuli (0.1-10 mA, 2 msec) applied to the skin receptive field. Further, DREZ stimulation blocked windup (a form of brief neuronal sensitization) to repetitive noxious stimuli (0.5 Hz) at 0-15 min in all groups (p < 0.05).
Attenuation of WDR neuronal activity may contribute to DREZ stimulation-induced analgesia. This finding supports the notion that DREZ may be a useful target for neuromodulatory control of pain.
近期临床研究表明，在背根入髓区（DREZ）进行神经刺激可能减轻神经性疼痛。然而，这种治疗效果的作用机制尚不清楚。在此，我们研究了DREZ刺激是否能抑制神经损伤大鼠脊髓广动力范围（WDR）神经元的活动。
我们对接受L5脊神经结扎（SNL）或假手术的大鼠进行了WDR神经元的体内细胞外单单位记录。通过测量DREZ刺激诱发坐骨神经Aα/β复合动作电位峰值而不诱发Aδ/C复合动作电位（即Ab1）的最低电流，我们将DREZ的双极电刺激（50Hz，0.2毫秒，5分钟）设置在仅激活Aα/β纤维的强度。
SNL大鼠（n = 25；数据合并自SNL后第14 - 16天[n = 15]和第45 - 75天[n = 10]的组）中WDR神经元升高的自发活动率在刺激后0 - 15分钟和30 - 45分钟时从刺激前水平显著降低（p < 0.01）。在假手术组（n = 8）和神经损伤大鼠中，DREZ刺激均减弱了施加于皮肤感受野的分级皮内电刺激（0.1 - 10 mA，2毫秒）诱发的WDR神经元反应的C成分，但不影响A成分。此外，DREZ刺激在所有组中均在0 - 15分钟时阻断了对重复有害刺激（0.5 Hz）的windup（一种短暂的神经元敏化形式）（p < 0.05）。
WDR神经元活动的减弱可能有助于DREZ刺激诱导的镇痛作用。这一发现支持了DREZ可能是疼痛神经调节控制的有用靶点这一观点。
