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系統識別號 U0026-2907201511345500
論文名稱(中文) 經皮神經電刺激對大鼠糖尿病神經病變性疼痛之影響
論文名稱(英文) Effects of transcutaneous electrical nerve stimulation (TENS) on diabetic neuropathic pain in rats
校院名稱 成功大學
系所名稱(中) 物理治療學系
系所名稱(英) Department of Physical Therapy
學年度 103
學期 2
出版年 104
研究生(中文) 賴奕儒
研究生(英文) Yi-Ju Lai
學號 T66011066
學位類別 碩士
語文別 英文
論文頁數 151頁
口試委員 指導教授-洪菁霞
口試委員-蔡昆霖
口試委員-陳郁文
中文關鍵字 經皮神經電刺激  糖尿病  痛覺異常  痛覺過度敏感 
英文關鍵字 transcutaneous electrical nerve stimulation  diabetes  allodynia  hyperalgeisa 
學科別分類
中文摘要 背景及目的:經皮神經電刺激可增加糖尿病病患的冷及熱疼痛閾並減輕病患的疼痛指數,然而對於經皮神經電刺激是如何減輕糖尿病所引發的神經性疼痛目前仍未可知。不過先前的研究已指出高血糖會改變腫瘤壞死因子α(TNF-α)、腫瘤壞死因子受體1(TNFR1)、腫瘤壞死因子受體2(TNFR2)、半胱氨酸蛋白酶3(Caspase-3)、磷脂酰肌醇3-激酶(PI3k)、蛋白質激酶 B(Akt)在周邊神經中的濃度。本篇研究主要是去探討經皮神經電刺激對於糖尿病鼠疼痛行為的影響並去了解上述物質在背根神經節、脊髓、坐骨神經及周邊神經的濃度變化情況。方法:將大鼠隨機分在五個不同的組別,分別為控制組、糖尿病組、糖尿病用高頻電刺激治療組、糖尿病用低頻電刺激治療組及糖尿病用交替高低頻電刺激治療組,治療組治療時間皆為每天三十分鐘,每周五天,一共治療三周。兩側的後腳觸覺及熱覺疼痛閾都會進行測量以比較治療前後的差異。在引發糖尿病後的第二十一天會將大鼠犧牲,之後會將相對應於腰椎第四到六節的脊髓後角、背根神經節、坐骨神經及周邊神經(脛神經、腓總神經及腓腸神經)取下進行組織分析。腫瘤壞死因子α的表現量是用酶聯免疫吸附試驗進行分析,而腫瘤壞死因子受體1、腫瘤壞死因子受體2、半胱氨酸蛋白酶3、磷脂酰肌醇3-激酶、蛋白質激酶 B則用西方點墨法測量。結果:單次治療後觸覺刺激反應閾及熱刺激反應閾的最高點在半小時到兩小時之間,二十四小時後反應閾會些微下降。在三周的治療中,經皮神經電刺激能有效的增加觸覺反應閾,但只有高頻電刺激能有效的增加熱刺激反應閾。腫瘤壞死因子α經過三周的經皮神經電刺激治療後在脊髓後角和背根神經節有顯著性的下降,不過在坐骨神經及周邊神經經過高頻及低頻電刺激治療後都是上升的,只有交替高低頻組的腫瘤壞死因子α在坐骨神經有下降。腫瘤壞死因子受體1、腫瘤壞死因子受體2、半胱氨酸蛋白酶3、磷脂酰肌醇3-激酶、蛋白質激酶 B在脊髓後角的含量在糖尿病組及三個治療組中是有上升的。在背根神經節中,腫瘤壞死因子受體1、腫瘤壞死因子受體2及蛋白質激酶 B在糖尿病組及三個治療組中是有上升的。到了坐骨神經,在糖尿病組中就只剩下腫瘤壞死因子受體2和磷脂酰肌醇3-激酶是上升的,而在周邊神經中則沒有物質是上升的。在三個治療組中,壞死因子受體1(TNFR1)和腫瘤壞死因子受體2在坐骨神經中有上升,在周邊神經只有壞死因子受體1上升。結論:三種不同頻率的經皮神經電刺激皆可減輕糖尿病所引起的觸覺異常性疼痛,但在腫瘤壞死因子α及其下游蛋白質濃度中交替高低頻電刺激治療組及低頻電刺激治療組較高頻電刺激組的影響更為顯著。
英文摘要 Background and Purpose: Transcutaneous electrical nerve stimulation (TENS) has been used to improve heat and cold pain thresholds and decrease the pain scales in diabetic patients. However, it remains unknown whether TENS could attenuate diabetic neuropathy. Previous research has shown that hyperglycemia could change the levels of TNF-α, TNFR1, TNFR2, cleaved caspase-3, p-Akt and p-PI3k in the PN. Thus, this study investigates the effects of TENS in the pain-like behaviors of the diabetic rats and the expression of TNF-α, TNFR1, TNFR2, cleaved caspase-3, p-Akt and p-PI3k in the DRG, SCDH, SN and PN. Methods: Five experimental groups consist of control, STZ, STZ+ HF TENS, STZ+ LF TENS, and STZ+ AF TENS. TENS will be delivered to the HF, LF and AF groups for 30 minutes per day and 5 days per week for 3 weeks. The mechanical and thermal pain thresholds have been tested under the rats’ hind paws of each side. The rats were sacrificed on the 21st day since the diabetic induction. After the 30-minute post-test period of the last treatment, the L4-L6 SCDH, DRGs, SN and PN (including tibial nerve, peroneal nerve and sural nerve) are collected for protein analysis. TNF-α levels were detected by Enzyme-linked Immunosorbent Assay (ELISA) and TNFR1, TNFR2, cleaved caspase-3, p-Akt and p-PI3k expressions were analyzed by Western Blot. Results: The peaks of the mechanical withdrawal threshold and thermal withdrawal latency are shown lasting after 30 minutes until 2 hours of treatment, but they slightly decreased after 24 hours. TENS can effectively increase the mechanical withdrawal threshold for 3 weeks. However, HF TENS only increases the thermal withdrawal latency for 3 weeks. TNF-α level in the spinal cord dorsal horn and dorsal root ganglions were suppressed after the 3-week TENS treatment, but it increased in the sciatic nerve and the peripheral nerve in both high and LF groups. TNF-α level in the sciatic nerve only decreased in the AF group. Expression of TNFR1, TNFR2, cleaved caspase-3, p-Akt and p-PI3k in the spinal cord dorsal horn significantly up-regulated in the STZ and treatment groups. Expressions of TNFR1, TNFR2 and p-Akt in dorsal root ganglion up-regulated in the STZ and treatment groups as well. However, only the expressions of TNFR2 and p-PI3k in sciatic nerve increased in the STZ group. The expressions of TNFR1 and TNFR2 in sciatic nerve and TNFR1 in peripheral nerve both enhanced in the treatment groups. Conclusion: HF, LF and AF TENS can all lower mechanical allodynia in diabetes, but the decrease in TNF-α level and cell proliferation and the increase of apoptosis in LF and AF groups are more significant than HF group.
論文目次 Abbreviations…………………………………………………………..I
Abstract………………………………………………………………...II
Chinese Abstract……………………………………………………….IV
誌謝………………………………………………………………...….VI
List of Figures…………………………………………………………VIII
List of Tables…………………………………………………………..XII
Introduction…………………………………………………………….1
Methods………………………………………………………………..5
Results…………………………………………………………………14
Discussion……………………………………………………………..19
Conclusion……………………………………………………………..23
References……………………………………………………………..24
Figures…………………………………………………………………30
Tables………………………………………………………………….149
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