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Long-term Therapeutic Effects of Extracorporeal Shock Wave-Assisted Melatonin Therapy on Mononeuropathic Pain in Rats

  • Chien-Hui Yang
  • Hon-Kan Yip
  • Hung-Fei Chen
  • Tsung-Cheng Yin
  • John Y. Chiang
  • Pei-Hsun Sung
  • Kun-Chen Lin
  • Yu-Huan Tsou
  • Yi-Ling Chen
  • Yi-Chen Li
  • Tien-Hung Huang
  • Chi-Ruei Huang
  • Chi-Wen Luo
  • Kuan-Hung ChenEmail author
Original Paper
  • 78 Downloads

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.

Keywords

Behavior test Dorsal root ganglion Spinal dorsal horn Protein kinase Inflammation Oxidative stress 

Notes

Acknowledgements

This study was supported by a program grant from Chang Gung Memorial Hospital, Chang Gung University (Grant Nos.: CMRPG8E0771, CMRPG8E1361).

Author Contributions

H-KY, C-HY and K-HC conceived of the study, and participated in the design of the study, data acquisition and analysis as well as drafting the manuscript. H-FC edited the manuscript. T-CY, JYC, P-H, K-CL and Y-LC were responsible for the laboratory assay and troubleshooting., Y-C, Ti-H, C-RH and CL participated in data acquisition, analysis, and interpretation. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Chien-Hui Yang
    • 1
  • Hon-Kan Yip
    • 2
    • 3
    • 4
    • 5
    • 6
  • Hung-Fei Chen
    • 7
  • Tsung-Cheng Yin
    • 8
  • John Y. Chiang
    • 9
  • Pei-Hsun Sung
    • 2
  • Kun-Chen Lin
    • 1
  • Yu-Huan Tsou
    • 1
  • Yi-Ling Chen
    • 2
  • Yi-Chen Li
    • 2
  • Tien-Hung Huang
    • 2
  • Chi-Ruei Huang
    • 2
  • Chi-Wen Luo
    • 2
  • Kuan-Hung Chen
    • 1
    • 4
    Email author
  1. 1.Department of AnesthesiologyKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiungTaiwan
  2. 2.Division of Cardiology, Department of Internal MedicineKaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineKaohsiungTaiwan
  3. 3.Institute for Translational Research in BiomedicineKaohsiung Chang Gung Memorial HospitalKaohsiungTaiwan
  4. 4.Center for Shockwave Medicine and Tissue EngineeringKaohsiung Chang Gung Memorial HospitalKaohsiungTaiwan
  5. 5.Department of Medical ResearchChina Medical University Hospital, China Medical UniversityTaichungTaiwan
  6. 6.Department of NursingAsia UniversityTaichungTaiwan
  7. 7.Institute of Technological and Vocational EducationNational Pingtung University of Science and TechnologyPingtungTaiwan
  8. 8.Department of Orthopaedic SurgeryKaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineKaohsiungTaiwan
  9. 9.Department of Computer Science and EngineeringNational Sun Yat-Sen UniversityKaohsiungTaiwan

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