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Long-term Therapeutic Effects of Extracorporeal Shock Wave-Assisted Melatonin Therapy on Mononeuropathic Pain in Rats |
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| Authors: | Yang Chien-Hui Yip Hon-Kan Chen Hung-Fei Yin Tsung-Cheng Chiang John Y Sung Pei-Hsun Lin Kun-Chen Tsou Yu-Huan Chen Yi-Ling Li Yi-Chen Huang Tien-Hung Huang Chi-Ruei Luo Chi-Wen Chen Kuan-Hung |
| Institution: | 1.Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Rd., Niaosong Dist, Kaohsiung, 83301, Taiwan ;2.Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan ;3.Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan ;4.Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 83301, Taiwan ;5.Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan ;6.Department of Nursing, Asia University, Taichung, 41354, Taiwan ;7.Institute of Technological and Vocational Education, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan ;8.Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan ;9.Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan ; |
| Abstract: | We evaluated the ability of extracorporeal shock wave (ECSW)-assisted melatonin (Mel) therapy to offer an additional benefit for alleviating the neuropathic pain (NP) in rats. Left sciatic nerve was subjected to chronic constriction injury (CCI) to induce NP. Animals (n?=?30) were randomized into group 1 (sham-operated control), group 2 (CCI only), group 3 (CCI?+?ECSW), group 4 (CCI?+?Mel) and group 5 (CCI?+?ECSW?+?Mel). By days 15, 22 and 29 after CCI, the thermal paw withdrawal latency (TPWL) and mechanical paw withdrawal threshold (MPWT) were highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, but they showed no difference between the later two groups (all p?<?0.0001). The protein expressions of inflammatory (TNF-α, NF-κB, MMP-9, IL-1ß), oxidative-stress (NOXs-1, -2, -4, oxidized protein), apoptotic (cleaved-caspase3, cleaved-PARP), DNA/mitochondrial-damaged (γ-H2AX/cytosolic-cytochrome C), microglia/astrocyte activation (ox42/GFAP), and MAPKs phosphorylated (p)-p38, p-JNK, p-ERK] biomarkers in dorsal root ganglia neurons (DRGs) and in spinal dorsal horn were exhibited an opposite pattern of TPWL among the five groups (all p?<?0.0001). Additionally, protein expressions of Nav.1.3, Nav.1.8 and Nav.1.9 in sciatic nerve exhibited an identical pattern to inflammation among the five groups (all p?<?0.0001). The numbers of cellular expressions of MAPKs (p-ERK1/2+/peripherin?+?cells, p-ERK1/2+/NF200?+?cells and p-JNK+/peripherin?+?cells, p-JNK+/NF200?+?cells) and voltage-gated sodium channels (Nav.1.8+/peripherin?+?cells, Nav.1.8+/NF200?+?cells, Nav.1.9+/peripherin?+?cells, Nav.1.9+/NF200?+?cells) in small and large DRGs displayed an identical pattern to inflammation among the five groups (all p?<?0.0001). In conclusion, the synergistic effect of combined ECSW-Mel therapy is superior to either one alone for long-term improvement of mononeuropathic pain-induced by CCI in rats. |
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