背景及目的: 持續的術後疼痛是在進行皮膚/肌肉-切開術(SMIR)後常見的問題。皮膚/肌肉-切開術的動物模型也被學界應用在研究術後造成淺層腓神經的神經性疼痛上。在臨床上，高頻/低頻經皮神經電刺激(TENS)也是常被用來處理術後造成的神經性疼痛，他主要透過門閾控制理論和啟動內啡肽的路徑來達到止痛效果。先前的研究指出低頻電刺激比起高頻電刺激在術後疼痛的控制上更為有效，但是是否在SMIR模型上有效則尚未知道。因此本研究的目的就在確認低頻TENS治療是否對於SMIR手術所造成的術後疼痛有有效的治療效果。
方法: 本研究的動物模型使用的是成年雄性SD大鼠，實驗組別分為: SMIR短期組(實驗為期一週)、SMIR長期組(實驗為期四週)、假手術控制組(儘切開未撐開)、SMIR+低頻TENS治療組、SMIR+低頻TENS治療+密集行為測試組。測試神經病理性疼痛的測試方式為使用von Frey纖毛測試機械性敏感度，以及Plantar儀器測試溫覺敏感度。TENS治療組的動物會接受每天一次、每周五次的TENS治療，參數設定為2Hz，脈衝頻寬100μs，持續20分鐘的治療。最後一次治療在術後七天進行。
結果: 接受SMIR手術的大鼠在術後第三天就在手術側出現了維持一周的短期觸覺過敏現象，而溫覺過敏的現象則維持了四週。觸覺過敏現象出現在了接收SMIR手術的大鼠雙側腳掌上，而溫覺過敏則主要集中在手術對側。在接受低頻TENS治療後的24小時中，低頻TENS的治療效果維持了大約4小時，但治療效果並沒有維持到24小時。接受低頻TENS的SMIR大鼠的縮回反應有明顯的減少，但是觸覺過敏的現象在不同的時間點產生恢復。在一週的低頻TENS治療期後，機械性過敏的現象在隔週就馬上恢復。另外，接受TENS治療的SMIR大鼠在雙側的痛覺過敏現象比起沒接受治療的SMIR都有得到改善。溫覺過敏的現象在三組之中的同側並沒有顯著的差異，但比起SMIR組低頻TENS治療還是在對側改善了症狀。
結論: SMIR手術在動物身上造成了明顯的痛覺過敏現象，接受低頻TENS治療後由SMIR手術所引起的術後疼痛得到明顯的壓制。基於本篇研究的結果，可建立未來在低頻TENS治療長期效果的研究和臨床應用。

Background and Purpose: Persistent postoperative pain is a common problem after the skin/muscle incision and retraction (SMIR) procedure. The SMIR model has been introduced to develop pain hypersensitivity from the saphenous nerve (SPN) injury leading to allodynia and hyperalgesia. Moreover, the transcutaneous electrical nerve stimulation (TENS) is a common clinical treatment that reduces neuropathic pain, and the applications of high-frequency (HF) and low-frequency (LF) TENS provide two theories of mechanisms. Previous studies have shown LF is less effective than HF in post-surgical pain and other models. However, its underlying mechanism suggests whether LF TENS is reliable for pain relief from the SMIR surgery remains unclear. Therefore, the purpose of this study is to determine the effects of LF TENS suppressing SMIR-induced postoperative pain in rats.
Methods: Male Sprague-Dawley rats were randomly assigned to the following groups: skin/muscle incision and retraction (SMIR) group (1 week), skin/muscle incision and retraction (SMIR) group (4 weeks), sham operation group, SMIR with LF TENS (SMIR+LF TENS) group (1 week), and SMIR with LF TENS (1 week) plus extensive behavior testing (SMIR+LF TENS) group. von Frey filaments and Hargreaves plantar apparatus were used to assess the symptoms of neuropathic pain. The SMIR+LF TENS groups received the TENS treatment set at 2 Hz and pulse width of 100 μs with a duration of 20 minutes per day (one time) and 5 days per week for one week. The rats received their last treatments on POD 7 since the SMIR surgery.
Results: The SMIR-operated rats displayed short-term mechanical allodynia and thermal hyperalgesia on the ipsilateral hind paw on POD 3 for one week, but long-lasting hyperalgesia persisted for four weeks after surgery (p<0.05). Tactile allodynia in the SMIR group was significantly increased than the sham group on both sides; whereas, thermal hyperalgesia occurred more on the contralateral side (p<0.05). During the 24-hour LF TENS treatment course, its therapeutic effect maintained shortly for about 4 hrs on POD 3 but did not persist for 24 hrs after treatment. The withdrawal responses of the SMIR+LF TENS group significantly decreased yet immediate effects of allodynia recovered at different time points (p<0.05). After the week-long LF TENS period, mechanical hypersensitivity recovered immediately on the following week. Furthermore, the SMIR+LF TENS group reduced tactile allodynia on both sides when compared to the SMIR group (p<0.05). No significant changes of thermal hyperalgesia were exhibited among the three groups on the ipsilateral side, but the LF TENS treatment improved on the contralateral side comparing to the SMIR group (p<0.05).
Conclusions: The SMIR surgery exhibited pain hypersensitivities during the week-long course, but short-term allodynia and long-term hyperalgesia were experienced during the month-long course. LF TENS suppressed the progression of mechanical allodynia evoked by the SMIR surgery. Future implications are to analyze more about the LF TENS-analgesic effect for the long-term phase and employ this treatment strategy to alleviate the symptoms of persistent post-surgical pain.

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