Chen Kuan-Hung, Yang Chien-Hui, Wallace Christopher Glenn, Lin Chung-Ren, Liu Chia-Kai, Yin Tsung-Cheng, Huang Tien-Hung, Chen Yi-Ling, Sun Cheuk-Kwan, Yip Hon-Kan
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung 83301, Taiwan, R.O.C.
Department of Plastic Surgery, University Hospital of South ManchesterManchester, UK.
Am J Transl Res. 2017 Oct 15;9(10):4593-4606. eCollection 2017.
This study tested the hypothesis that combination therapy using extracorporeal shock wave (ECSW)-melatonin (Mel) was superior to either alone at ameliorating neuropathic pain (NP). NP was induced by chronic constriction injury (CCI) to the left sciatic nerve in rats. Animals were categorized into sham control (group 1), CCI only (group 2), CCI-ECSW (group 3), CCI-Mel (group 4) and CCI-ECSW-Mel (group 5). By days 2 and 8 after CCI, the mechanical paw withdrawal threshold (MPWT)/thermal paw withdrawal latency (TPWL) were highest in group 2, lowest in group 1, significantly lower in group 5 than in groups 3 and 4 (all p<0.0001), and not significantly different between groups 3 and 4. The protein expressions of inflammatory (TNF-α/NF-κB/MMP-9/IL-1ß/GFAP/ox42), oxidative-stress (NOX-1/NOX-2/NOX-4/oxidized protein), DNA/mitochondrial-damaged (γ-H2AX/cytosolic mitochondria), apoptotic (cleaved capase-3/PARP), and MAPK family biomarkers (p-P38/p-JNK/p-ERK1/2) in dorsal root ganglia and spinal dorsal horn expressed a similar pattern of MPWT/TPWL among the five groups, except for significantly higher in group 4 than in group 3 (all p<0.0001). The protein expressions of Nav.1.3, Nav.1.8 and Nav.1.9 in sciatic nerve displayed an identical pattern to inflammation among the five groups (all p<0.001). Pain facilitated cellular expressions (p-P38+/peripherin+ cells, P38+/NF200+ cells) displayed an identical pattern to inflammation among the five groups (all p<0.0001). In conclusion, ECSW-Mel combination therapy markedly ameliorated NP induced by CCI.
使用体外冲击波（ECSW）-褪黑素（Mel）的联合疗法在改善神经性疼痛（NP）方面优于单独使用ECSW或Mel。通过对大鼠左侧坐骨神经进行慢性缩窄损伤（CCI）来诱导NP。将动物分为假手术对照组（第1组）、仅CCI组（第2组）、CCI-ECSW组（第3组）、CCI-Mel组（第4组）和CCI-ECSW-Mel组（第5组）。在CCI后第2天和第8天，机械性缩爪阈值（MPWT）/热缩爪潜伏期（TPWL）在第2组中最高，在第1组中最低，第5组显著低于第3组和第4组（均p<0.0001），第3组和第4组之间无显著差异。背根神经节和脊髓背角中炎症（TNF-α/NF-κB/MMP-9/IL-1ß/GFAP/ox42）、氧化应激（NOX-1/NOX-2/NOX-4/氧化蛋白）、DNA/线粒体损伤（γ-H2AX/胞质线粒体）、凋亡（裂解的半胱天冬酶-3/PARP）和MAPK家族生物标志物（p-P38/p-JNK/p-ERK1/2）的蛋白表达在五组中呈现出与MPWT/TPWL相似的模式，除了第4组显著高于第3组（均p<0.0001）。坐骨神经中Nav.1.3、Nav.1.8和Nav.1.9的蛋白表达在五组中呈现出与炎症相同的模式（均p<0.001）。疼痛促进细胞表达（p-P38+/外周蛋白+细胞，P38+/NF200+细胞）在五组中呈现出与炎症相同的模式（均p<0.0001）。总之，ECSW-Mel联合疗法显著改善了CCI诱导的NP。
