Millennium Pain Center, Bloomington, IL, USA.
Department of Psychology, Illinois Wesleyan University, Bloomington, IL, USA.
Neuromodulation. 2020 Jan;23(1):26-35. doi: 10.1111/ner.12964. Epub 2019 May 9.
To investigate the effect of phase polarity and charge balance of spinal cord stimulation (SCS) waveforms on pain behavior and gene expression in a neuropathic pain rodent model. We hypothesized that differing waveforms will result in diverse behavioral and transcriptomics expression due to unique mechanisms of action.
Rats were implanted with a four-contact cylindrical mini-lead and randomly assigned to two control (no-pain and pain model) and five test groups featuring monophasic, as well as charge-unbalanced and charge-balanced biphasic SCS waveforms. Mechanical and cold allodynia were assessed to measure efficacy. The ipsilateral dorsal quadrant of spinal cord adjacent to the lead was harvested post-stimulation and processed to determine gene expression via real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Gene expression, SCS intensity (mA), and behavioral score as percent of baseline (BSPB) were statistically analyzed and used to generate correlograms using R-Studio. Statistical analysis was performed using SPSS22.0, and p < 0.05 was considered significant.
As expected, BSPB was significantly lower for the pain model group compared to the no-pain group. BSPB was significantly improved post-stim compared to pre-stim using cathodic, anodic, symmetric biphasic, or asymmetric biphasic 1:2 waveforms; however, BSPB was not restored to Sham levels. RT-PCR analysis showed that eight genes demonstrated a significant difference between the pain model and SCS waveforms and between waveforms. Correlograms reveal a linear correlation between regulation of expression of a given gene in relation to mA, BSPB, or other genes.
Our results exhibit that specific SCS waveforms differentially modulate several key transcriptional pathways that are relevant in chronic pain conditions. These results have significant implications for SCS: whether to move beyond traditional paradigm of neuronal activation to focus also on modulating immune-driven processes.
研究脊髓刺激（SCS）波形的相位极性和电荷平衡对神经病理性疼痛啮齿动物模型的疼痛行为和基因表达的影响。我们假设，由于作用机制不同，不同的波形将导致不同的行为和转录组表达。
大鼠植入了一个四接触圆柱形微型导联，并随机分配到两个对照组（无痛和疼痛模型）和五个测试组，分别具有单相以及电荷不平衡和电荷平衡双相 SCS 波形。通过评估机械性和冷感觉异常来测量疗效。刺激后采集与导联相邻的同侧背象限脊髓，并进行处理，通过实时逆转录聚合酶链反应（RT-PCR）确定基因表达。使用 R-Studio 对基因表达、SCS 强度（mA）和行为评分相对于基线的百分比（BSPB）进行统计分析，并生成相关图。使用 SPSS22.0 进行统计分析，p<0.05 被认为具有统计学意义。
正如预期的那样，与无痛组相比，疼痛模型组的 BSPB 明显降低。与刺激前相比，使用阴极、阳极、对称双相或非对称双相 1:2 波形刺激后，BSPB 显著改善；然而，BSPB 并未恢复到 Sham 水平。RT-PCR 分析显示，在疼痛模型和 SCS 波形之间以及在波形之间，有 8 个基因表现出显著差异。相关图显示，在给定基因的表达调控与 mA、BSPB 或其他基因之间存在线性相关性。
我们的结果表明，特定的 SCS 波形可差异调节与慢性疼痛状况相关的几个关键转录途径。这些结果对 SCS 具有重要意义：是否超越传统的神经元激活范式，也关注调节免疫驱动的过程。
