From the *Basic Science Research, Millennium Pain Center, Bloomington; †School of Biological Sciences, Illinois State University, Normal; ‡Medical School, University of Illinois at Urbana-Champaign, Urbana; and §Department of Psychology, Illinois Wesleyan University, Bloomington, IL.
Reg Anesth Pain Med. 2017 Mar/Apr;42(2):246-251. doi: 10.1097/AAP.0000000000000550.
Spinal cord stimulation (SCS) has been shown to influence pain-related genes in the spinal cord directly under the stimulating electrodes. There is limited information regarding changes occurring at the dorsal root ganglion (DRG). This study evaluates gene expression in the DRG in response to SCS therapy.
Rats were randomized into experimental or control groups (n = 6 per group). Experimental animals underwent spared-nerve injury, implantation of lead, and continuous SCS (72 hours). Behavioral assessment for mechanical hyperalgesia was conducted to compare responses after injury and treatment. Ipsilateral DRG tissue was collected, and gene expression quantified for interleukin 1b (IL-1b), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), GABA B receptor 1 (GABAbr1), substance P (subP), Integrin alpha M (ITGAM), sodium/potassium ATP-ase (Na/K ATPase), fos proto-oncogene (cFOS), serotonin receptor 3A (5HT3r), galanin (Gal), vasoactive intestinal peptide (VIP), neuropeptide Y (NpY), glial fibrillary acidic protein (GFAP), and brain derived neurotropic factor (BDNF) via quantitative polymerase chain reaction. Statistical significance was established using analysis of variance (ANOVA), independent t tests, and Pearson correlation tests.
Expression of IL-1b and IL-6 was reversed following SCS therapy relative to the increase caused by the injury model. Both GABAbr1 and Na/K ATPase were significantly up-regulated upon implantation of the lead, and SCS therapy reversed their expression to within control levels. Pearson correlation analyses reveal that GABAbr1 and Na/K ATPase expression was dependent on the stimulating current intensity.
Spinal cord stimulation modulates expression of key pain-related genes in the DRG. Specifically, SCS led to reversal of IL-1b and IL-6 expression induced by injury. Interleukin 6 expression was still significantly larger than in sham animals, which may correlate to residual sensitivity following continuous SCS treatment. In addition, expression of GABAbr1 and Na/K ATPase was down-regulated to within control levels following SCS and correlates with applied current.
脊髓刺激（SCS）已被证明可直接影响刺激电极下方脊髓中的疼痛相关基因。关于背根神经节（DRG）发生的变化，信息有限。本研究评估了 SCS 治疗对 DRG 中基因表达的影响。
将大鼠随机分为实验组和对照组（每组 6 只）。实验组动物接受神经保留性损伤、植入导联和连续 SCS（72 小时）。进行机械性痛觉过敏行为评估，以比较损伤和治疗后的反应。收集同侧 DRG 组织，通过定量聚合酶链反应定量检测白细胞介素 1b（IL-1b）、白细胞介素 6（IL-6）、肿瘤坏死因子α（TNF-α）、γ-氨基丁酸 B 受体 1（GABAbr1）、P 物质（subP）、整合素α M（ITGAM）、钠/钾 ATP 酶（Na/K ATPase）、原癌基因 fos（cFOS）、血清素受体 3A（5HT3r）、甘丙肽（Gal）、血管活性肠肽（VIP）、神经肽 Y（NpY）、胶质纤维酸性蛋白（GFAP）和脑源性神经营养因子（BDNF）的表达。采用方差分析（ANOVA）、独立 t 检验和 Pearson 相关检验确定统计学意义。
与损伤模型引起的增加相比，SCS 治疗后 IL-1b 和 IL-6 的表达得到逆转。GABAbr1 和 Na/K ATPase 在植入导联后均显著上调，SCS 治疗将其表达逆转至对照水平。Pearson 相关分析显示，GABAbr1 和 Na/K ATPase 的表达依赖于刺激电流强度。
脊髓刺激调节 DRG 中关键疼痛相关基因的表达。具体来说，SCS 导致损伤诱导的 IL-1b 和 IL-6 表达逆转。白介素 6 的表达仍然明显大于假手术动物，这可能与连续 SCS 治疗后的残留敏感性相关。此外，SCS 后 GABAbr1 和 Na/K ATPase 的表达下调至对照水平，并与应用电流相关。
