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



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.



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.



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.
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.
Po-Ching
PC
Huang
Kun-Ling
KL
Tsai
Yu-Wen
YW
Chen
Heng-Teng
HT
Lin
Ching-Hsia
CH
Hung
D000818:Animals; D001522:Behavior, Animal; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D015536:Down-Regulation; D005081:Exercise Therapy; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012585:Sciatica / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014464:Ultrasonic Therapy; D015854:Up-Regulation
D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10