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Exercise Combined With Ultrasound Attenuates Neuropathic Pain in Rats Associated With Downregulation of IL-6 and TNF-a, but With Upregulation of IL-10

Huang, Po-Ching MS*; Tsai, Kun-Ling PhD*; Chen, Yu-Wen PhD†‡; Lin, Heng-Teng MD§∥; Hung, Ching-Hsia PhD

doi: 10.1213/ANE.0000000000001600
Pain and Analgesic Mechanisms: Original Clinical Research Report

BACKGROUND: Although there are several evidences that suggest efficacies of therapeutic ultrasound (TU) or treadmill exercise (TE) to alleviate nerve injury—associated pain, molecular mechanisms are less clear. We aimed to investigate the impact of TU and/or TE on neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve and their roles of proinflammatory and anti-inflammatory cytokines.

METHODS: Rats were randomly divided into (n = 10 per group) sham operation (sham), CCI procedure followed by false application of TU (CCI + TU0), CCI procedure followed by false application of TU and TE (CCI + TU0 + TE), CCI, and CCI procedure followed by TU alone (CCI + TU), TE alone (CCI + TE), or both TU and TE (CCI + TU + TE) groups. TU and TE were administered daily, starting on postoperative day 8 (POD 8) for 3 weeks. Mechanical and thermal hypersensitivity, tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and IL-6 in the sciatic nerve were assessed on PODs 14 and 28. Data were analyzed by 1-way, 2-way, or 3-way analysis of variance of repeated measures or 1-way analysis of variance.

RESULTS: After the interventions, there was statistical significance (all P ≤ .0001) between the groups for all outcome parameters, all in favor of the experimental group: 4.2 for mean mechanical withdrawal thresholds (95% confidence interval, 1.8–7.6) and 4.8 for mean thermal withdrawal latencies (95% confidence interval, 2.2–8.1). TU and/or TE provoked an increase in mechanical withdrawal thresholds and thermal withdrawal latencies in CCI rats. TU + TE was more effective to reverse pain hypersensitivity than having each treatment alone. On PODs 14 and 28, the CCI rats exhibited an upregulation of sciatic TNF-α and IL-6 expression, whereas TU or TE alone or TU + TE combination prevented the upregulation. TU and/or TE also showed the upregulation of less IL-10 expression in the sciatic nerve.

CONCLUSIONS: We found that TU + TE is better than TU or TE alone for treating neuropathic pain. TU and/or TE for pain management may be straightly associated with less TNF-α and IL-6 expression and more IL-10 expression.

Published ahead of print March 17, 2017.

From the *Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Health Care, China Medical University, Taichung, Taiwan; Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; §Department of Physical Medicine and Rehabilitation, Madou Sin-Lau Hospital, Tainan, Taiwan; Department of Nursing, Chung Hwa University of Medical Technology, Tainan, Taiwan; and the Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Published ahead of print March 17, 2017.

Accepted for publication July 25, 2016.

Funding: Supported by grant MSLH-105-03 from Madou Sin-Lau Hospital, Tainan, Taiwan.

The authors declare no conflicts of interest.

Drs. Lin and Huang contributed equally to this work.

Reprints will not be available from the authors.

Address correspondence to Ching-Hsia Hung, PhD, Department of Physical Therapy, National Cheng Kung University, College of Medicine, No.1 Ta-Hsueh Rd, Tainan 701, Taiwan. Address e-mail to

© 2017 International Anesthesia Research Society
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