神經疼痛(neuropathic pain)為佔有世界總人口數百分之七罹患率的神經性疾病。臨床上，常見之治療方法包含投藥與經皮神經電刺激(transcutaneous electrical nerve stimulation)。然而，物理治療常用之超音波治療(ultrasound therapy, USD)對於神經性疼痛療效之科學證據，至今仍匱乏不足。先前亦有研究結果指出，給予神經疼痛之實驗大鼠長期跑步機運動(treadmill exercise, TME)訓練，得以緩解其症狀。綜合以上所述，本研究主在探討超音波治療之效果，以及結合超音波與跑步機運動對於神經性疼痛改善之成效。實驗採用坐骨神經慢性壓迫性損傷(chronic constriction injury, CCI)之動物模型，將大鼠隨機分至五組：控制組(Sham)、慢性壓迫性神經損傷組(CCI)、慢性壓迫性神經損傷合併超音波治療組(CCI+USD)、慢性壓迫性神經損傷合併跑步機運動組(CCI+TME)、慢性壓迫性神經損傷合併跑步機運動與超音波治療組(CCI+TME+USD)。超音波治療組使用一兆赫之治療探頭，以一瓦每平方公分之強度、百分之百工作週期、於受損處上方實行五分鐘治療；跑步機運動組在術後休息一周後開始進行，速度定在十四到六公尺每分鐘，配合百分之八傾斜角，進行三十分鐘之跑步機運動。以上治療每周實行五次。腳底熱覺測試(Plantar Test) 與觸覺計(Von Frey Hair Aesthesiometer)用以測量熱痛過敏(Thermal hyperalgesia)和機械性痛覺超敏 (mechanical allodynia)之表現，判定神經性疼痛之程度。於犧牲後將坐骨神經與其分支神經、第四至第六腰椎之脊髓與背根神經節取下並進行生化指標表現量分析，包含腫瘤壞死因子-α (tumor necrosis factor-α, TNF-α)，介白素-6 (interleukin-6, IL-6)、介白素-10 (interleukin-10, IL-10)、神經膠質細胞之生物指標─離子鈣接頭抗體-1 (ionized calcium-binding adapter molecule-1, IBA-1)與P物質(substance P)及其受體─神經激肽-1受體(Neurokinin-1 receptor, NK-1R)之含量分析。實驗結果顯示，經過四周介入後，跑步機運動組與合併治療組比起控制組體重顯著較低，而跑步機運動組比起慢性壓迫性神經損傷組體重同樣顯著較低；於熱痛敏感測試與機械性痛覺超敏測試中，慢性壓迫性神經損傷鼠之表現明顯較控制鼠為差。超音波治療、跑步機運動與合併處理，表現皆較慢性壓迫性神經損傷鼠為佳；其中，合併處理組之表現較超音波治療與跑步機運動訓練組為高，而超音波治療組與跑步機運動訓練組則無差異。經過四周治療後，控制鼠與合併處理組在熱痛敏感表現與機械性痛覺超敏測試上並無差異。在生化分析部分，腫瘤壞死因子-α在坐骨神經之跑步機運動組與合併治療組較慢性壓迫性損傷組顯著較低；介白素-6在坐骨神經之跑步機運動組與合併治療組較控制組顯著較低；介白素-10在坐骨神經之慢性壓迫性損傷組與合併治療組較控制組為高；其餘生化數據無差異。
綜歸以上，超音波治療可有效地降低神經性疼痛，而合併跑步機運動訓練更可大幅度降低神經性疼痛之程度。

Neuropathic pain is a common neurological disorder which affects 7% of general population. Clinical interventions included medication and electrical stimulation. However, the effect of ultrasound treatment remains unclear. Also, previous report suggested that treadmill exercise alleviated neuropathic symptoms. Therefore, we investigated the effect of ultrasound treatment and the outcome of combining treadmill exercise and ultrasound treatment in chronic constriction injury (CCI) induced neuropathic rats in this study. We provided a constricted injury on rat’s sciatic nerve. Rats were randomly assigned to five groups: sham operation, CCI, CCI with ultrasound treatment (CCI+USD), CCI with treadmill exercise treatment (CCI+TME), and CCI with combine treatment (CCI+TME+USD). Ultrasound group using 1 MHz probe with 1 w/cm2 and 100% on-off cycle, gently apply on the skin surface for 5 minutes, 5 days/week for 4 weeks; treadmill exercise group receiving a week off after surgery, the exercise started at day 7 and the parameter set at 14-16 m/min with 8% incline grade for 30 minutes, 5 days/week for 3 weeks. Thermal hyperalgesia and mechanical allodynia were used to determine the level of neuropathic pain by using Plantar Test and Von Frey Aesthesiometer, respectively. After sacrifice, sciatic nerve and branch of sciatic nerve, spinal cord and dorsal root ganglions were harvested and prepared for determining the expression of cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10), ionized calcium-binding adapter molecule-1 (IBA-1), neurotransimitter substance P and its receptor neurokini-1 receptor (NK-1R). In thermal hyperalgesia and mechanical allodynia, we found that i) the withdrawal latency (WL) and withdrawal threshold (WT) of CCI group was shorter than sham ones; ii) all three treatments groups increased the responses of WL and WT; iii) the WL and WT of CCI+TME+USD group was higher than CCI+USD or CCI+TME groups and there were no difference between CCI+USD and CCI+TME groups; iv) after 4-weeks intervention, the WL and WT were indistinguishable between sham and CCI+TME+USD group. In TNF-α, the CCI+TME and CCI+TME+USD groups were lower than CCI group in sciatic nerve; in IL-6, the CCI+TME and CCI+TME+USD groups were lower than sham group in sciatic nerve; in IL-10, the CCI and CCI+TME+USD groups were higher than sham group in sciatic nerve. In conclusion, ultrasound treatment reduced neuropathic pain and combination of ultrasound and treadmill exercise could even provide a better outcome.

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