Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United States.
Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, United States.
Pain. 2021 Dec 1;162(12):2917-2932. doi: 10.1097/j.pain.0000000000002284.
Dorsal root ganglion field stimulation (GFS) relieves evoked and spontaneous neuropathic pain by use-dependent blockade of impulse trains through the sensory neuron T-junction, which becomes complete within less than 1 minute for C-type units, also with partial blockade of Aδ units. We used this tool in the spinal nerve ligation (SNL) rat model to selectively block sensory neuron spontaneous activity (SA) of axotomized neurons at the fifth lumbar (L5) level vs blockade of units at the L4 level that remain uninjured but exposed to inflammation. In vivo dorsal root single-unit recordings after SNL showed increased SA in L5 units but not L4 units. Ganglion field stimulation blocked this SA. Ganglion field stimulation delivered at the L5 dorsal root ganglion blocked mechanical hyperalgesia behavior, mechanical allodynia, and ongoing spontaneous pain indicated by conditioned place preference, whereas GFS at L4 blocked evoked pain behavior but not spontaneous pain. In vivo single-unit recordings of spinal cord dorsal horn (DH) wide-dynamic-range neurons showed elevated SA after SNL, which was reduced by GFS at the L5 level but not by GFS at the L4 level. In addition, L5 GFS, but not L4 GFS, increased mechanical threshold of DH units during cutaneous mechanical stimulation, while L5 GFS exceeded L4 GFS in reducing evoked firing rates. Our results indicate that SA in injured neurons supports increased firing of DH wide-dynamic-range neurons, contributing to hyperalgesia, allodynia, and ongoing pain. Ganglion field stimulation analgesic effects after nerve injury are at least partly attributable to blocking propagation of this SA.
背根神经节场刺激 (GFS) 通过感觉神经元 T 结对冲动列车进行依时阻断，从而缓解诱发性和自发性神经病理性疼痛，C 型单位在不到 1 分钟内即可完全阻断，Aδ 型单位也可部分阻断。我们在脊神经结扎 (SNL) 大鼠模型中使用该工具，选择性地阻断 L5 水平轴突切断神经元的感觉神经元自发性活动 (SA)，而对未受伤但暴露于炎症中的 L4 水平的单位进行阻断。SNL 后活体背根单个单位记录显示 L5 单位的 SA 增加，但 L4 单位没有。神经节场刺激阻断了这种 SA。在 L5 背根神经节进行神经节场刺激可阻断机械性痛觉过敏行为、机械性痛觉过敏和由条件性位置偏好表示的持续性自发性疼痛，而 L4 处的 GFS 则阻断诱发性疼痛行为但不阻断自发性疼痛。SNL 后脊髓背角 (DH) 宽动态范围神经元的活体单单位记录显示 SA 升高，L5 水平的 GFS 可降低 SA，但 L4 水平的 GFS 则不能。此外，L5 GFS 可增加 DH 单位在皮肤机械刺激期间的机械阈值，而 L5 GFS 可降低诱发性放电率，其效果优于 L4 GFS。我们的结果表明，损伤神经元的 SA 支持 DH 宽动态范围神经元的放电增加，从而导致痛觉过敏、痛觉过敏和持续性疼痛。神经损伤后的神经节场刺激镇痛效果至少部分归因于阻断这种 SA 的传播。
