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研究生:黃書鴻
研究生(外文):Shu-Hung Huang
論文名稱:自體脂肪移植治療燙傷導致神經性疼痛的成效與探討:從基礎到臨床
論文名稱(外文):Autologous fat graft injection for treatment of burns induced neuropathic pain: From bench to clinical
指導教授:賴春生賴春生引用關係
指導教授(外文):CHUNG-SHENG LAI
學位類別:博士
校院名稱:高雄醫學大學
系所名稱:醫學研究所博士班
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2015
畢業學年度:104
語文別:英文
論文頁數:122
中文關鍵詞:脂肪神經性疼痛燙傷
外文關鍵詞:fat graftneuropathic painburn
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異常感覺痛在燒燙傷的患者其傷口癒合後是常見的現象,且難以治癒。現有的藥物通常效果不好,也常出現副作用,因此此種疼痛的治療仍然是個重要的臨床議題。
自體脂肪移植最近的研究顯示在臨床上局部注射在乳房切除術後疼痛與在阿諾德神經痛(Arnold neuralgia) 都能改善疼痛。甚至在放射線造成的皮膚發炎反應經過脂肪移植之後也可改善發炎與纖維化。這些機轉仍然不明,需要更多的研究來探討脂肪移植的對疼痛機轉。
在本研究中,主要分為三部分,第一部分: 利用大鼠來建立足底皮膚三度燙燒傷引發神經性疼痛的動物模型,先由主觀動物行為觀察其疼痛反應,並確定足底疤痕組織變化及相對應的皮節脊髓之微小膠質細胞(microglia)因疼痛而的活化,後續將老鼠鼠蹊脂肪移植注射到疤痕位置,發現其主觀的行為疼痛反應改善與客觀的微小膠質細胞活性減少,由此可知自體脂肪移植注射至疤痕可以改善疤痕疼痛。第二部分:進一步探討自體脂肪移植後疤痕疼痛改善的情形,發現疤痕皮膚與其向對應的皮節脊髓發炎蛋白表現如(COX-2, iNOS, and nNOS)因為脂肪移植而降低且與脊髓星狀神經細胞的發炎(reduced p-NFκB activation)反應與凋亡都有降低的情形,因此我們推論自體脂肪移植降低了疤痕的發炎反應進而改善疼痛。第三部分,在整形外科使用脂肪移植是很常見的手術方法,我們取患者的自體脂肪注射於頑固性疼痛疤痕中,並評估其治療效果,發現術後一個禮拜開始有改善的情形,且在追蹤過程中持續有效長達19個月。
根據以上三個部分的研究成果顯示,自體脂肪移植注射於疼痛性疤痕可以改善疤痕疼痛。


Allodynia is a common phenomenon in patients with burn wounds, which is difficult to cure and will continue for years. This kind of chronic pain has poor response with current medical treatments and may have side effects with the medication provided. Thus, management of burn induced neuropathic pain is an important issue in clinical practice.
 Autologous fat grafting has recently been shown to improve neuropathic pain in patients with postmastectomy pain syndrome and Arnold neuralgia. The other studies demonstrate that fat grafting can attenuate inflammation in radiodermatitis and slow fibrosis. However, the mechanisms involved in autologous fat grafting are still unknown so further research is needed.
This thesis is divided to three parts. In the first part, we established that the 3rd degree hind paw burn of a rat induced neuropathic pain, which is confirmed by the subjective behavior test and microglia activation in corresponding dermatome spinal cord dorsal horn. After we confirmed this animal model, we harvested autologous inguinal fat graft and injected it into the wound. Results showed that fat graft is effective in treating neuropathic pain.
In the second part, we further focus on the mechanisms of how fat graft alleviated neuropathic pain. Our results show that the inflammatory COX-2, iNOS, and nNOS proteins in the hind paw scar and corresponding dermatome spinal cords are significantly attenuated after the fat graft injection. Further fat grafts also reduced the p-NFκB expression and attenuated apoptosis in the spinal cord dorsal horns. We speculate that the fat graft reduced inflammation and further alleviated neuropathic pain.
In the third part, autologous fat grafting is a daily practice in plastic surgery. We harvested autologous fat grafts, then injected it into the refractory painful scar, and evaluated the effect of pain relief. The data showed a week after the operation, and the pain alleviated and proved effective for up to 19 months.

According to the above findings, we conclude that the injection of autologous fat graft in the neuropathic scar is effective with alleviating pain.

Key word: fat graft, neuropathic pain, burn


目錄
中文摘要 ............................................................................................................................................. 2
英文摘要 ............................................................................................................................................. 3
玫謝辭 ................................................................................................................................................. 4
Introduction ....................................................................................................................................... 6
Part one: ........................................................................................................................................... 12
Autologous Fat Grafting Alleviates Burn-induced Neuropathic Pain in Rats .................. 12
Introduction ............................................................................................................................................... 13
Methods ....................................................................................................................................................... 14
Results .......................................................................................................................................................... 20
Discussion .................................................................................................................................................... 28
Part two: ........................................................................................................................................... 33
Fat Grafting in Burn Scar Alleviates Neuropathic Pain via Anti-inflammation Effect in
Scar and Spinal Cord ..................................................................................................................... 33
Introduction: .............................................................................................................................................. 34
Materials and Methods ............................................................................................................................. 36
Results .......................................................................................................................................................... 41
Discussion .................................................................................................................................................... 51
Conclusions ................................................................................................................................................. 53
Part three: ........................................................................................................................................ 55
Alleviation of Neuropathic Scar Pain Using Autologous Fat Grafting ............................... 55
Introduction ............................................................................................................................................... 56
Methods ....................................................................................................................................................... 58
Results .......................................................................................................................................................... 62
Conclusion .................................................................................................................................................. 72
References: ....................................................................................................................................... 76
Related publish meant .................................................................................................................... 89

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