Dorsal Root Ganglion Stimulation Alleviates Pain-related Behaviors in Rats with Nerve Injury and Osteoarthritis.
Dorsal Root Ganglion Stimulation Alleviates Pain-related Behaviors in Rats with Nerve Injury and Osteoarthritis.
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DOI：
10.1097/aln.0000000000003348
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发表时间：
2020-08
期刊：
影响因子：
8.8
通讯作者：
Pan B
中科院分区：
文献类型：
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作者：
Yu G;Segel I;Zhang Z;Hogan QH;Pan B
背根神经节野刺激是临床上使用的一种镇痛神经调节方法，但其机制尚不清楚，因为还没有得到证实的动物模型。作者假设神经节刺激在减少临床前慢性疼痛模型中的疼痛行为方面是有效的。作者对有创伤性神经病(胫神经损伤)、膝关节内注射碘乙酸单钠诱发的骨性关节炎或无损伤的大鼠(幼稚)提供神经节刺激或脊髓刺激。通过测试一系列与疼痛相关的反射、功能和情感行为来评估止痛效果。在有神经损伤的大鼠中，多水平L4和L5神经节刺激对机械伤害性刺激的敏感性(曲线下面积，−1,447±423min x%反应；n=12)比单水平神经节刺激L4和L5(−960±251min x%反应；n=8；P=0.012)和L5([−676±295min x%反应；n=8；P<；0.0001]vs.L4和L5)更能降低痛性机械刺激的敏感性。L4(−93±65 S)、L5(−57±36 S)和多水平L5(−81±68 S vs S：90±76 S；P=0.003；n=8)。在骨关节炎大鼠中，多水平L3和L4神经节刺激降低膝关节运动敏感性(−156±28minx点；n=8)比L3(屈膝试验中−94±19minx点；n=7；P=0.002)或L4([−71±22minx点；n=7；P<；0.0001]vs.L3和L4)更明显。骨性关节炎的条件性位置偏爱在L3(−78±77 S比实验[68±136S]；P=0.048；n=9)、L4(−96±51 S比实验[73±111 S]；P=0.004；n=9)和L3和L4(实验前[−69±52 S；n=7]比实验[55±140 S]；P=0.022；n=7)时表现出对神经节刺激的镇痛效果。背根神经节刺激在神经病理性和骨性关节炎的临床前疼痛模型中是有效的，证明了神经节刺激在无安慰剂环境下的有效性，并证明该模型是适合于机制研究的平台。
Dorsal root ganglion field stimulation is an analgesic neuromodulation approach in use clinically, but its mechanism is unknown as there is no validated animal model for this purpose. The authors hypothesized that ganglion stimulation is effective in reducing pain-like behaviors in preclinical chronic pain models. The authors provided ganglion stimulation or spinal cord stimulation to rats with traumatic neuropathy (tibial nerve injury), or osteoarthritis induced by intraarticular knee monosodium iodoacetate, or without injury (naïve). Analgesia was evaluated by testing a battery of pain-related reflexive, functional, and affective behaviors. In rats with nerve injury, multilevel L4 and L5 ganglion stimulation decreased hypersensitivity to noxious mechanical stimulation more (area under curve, −1,447 ± 423 min x % response; n = 12) than single level ganglion stimulation at L4 ([−960 ± 251 min x % response; n = 8; P = 0.012] vs. L4 and L5), and L5 ([−676 ± 295 min x % response; n = 8; P < 0.0001] vs. L4 and L5). Spontaneous pain-like behavior, evaluated by conditioned place preference, responded to single L4 (Pretest [−93 ± 65 s] vs. Test [87 ± 82 s]; P = 0.002; n = 9), L5 (Pretest [−57 ± 36 s] vs. Test [137 ± 73 s]; P = 0.001; n = 8), and multilevel L4 and L5 (Pretest: −81 ± 68 s vs. Test: 90 ± 76 s; P = 0.003; n = 8) ganglion stimulation. In rats with osteoarthritis, multilevel L3 and L4 ganglion stimulation reduced sensitivity to knee motion more (−156 ± 28 min x points; n = 8) than L3 ([−94 ± 19 min x points in knee bend test; n = 7; P = 0.002] vs. L3 and L4) or L4 ([−71 ± 22 min x points; n = 7; P < 0.0001] vs. L3 and L4). Conditioned place preference during osteoarthritis revealed analgesic effectiveness for ganglion stimulation when delivered at L3 (Pretest [−78 ± 77 s] vs. Test [68 ± 136 s]; P = 0.048; n = 9), L4 (Pretest [−96 ± 51 s] vs. Test [73 ± 111 s]; P = 0.004; n = 9), and L3 and L4 (Pretest [−69 ± 52 s; n = 7] vs. Test [55 ± 140 s]; P = 0.022; n = 7). Dorsal root ganglion stimulation is effective in neuropathic and osteoarthritic preclinical rat pain models with peripheral pathologic origins, demonstrating effectiveness of ganglion stimulation in a placebo-free setting and justifying this model as a suitable platform for mechanistic studies.