全期睡眠剝奪對大白鼠疼痛反應及脊髓c-fos基因表現之影響; Effects of Total Sleep Deprivation on Nociceptive Response and Spinal c-fos Expression in Rats

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Title:	全期睡眠剝奪對大白鼠疼痛反應及脊髓c-fos基因表現之影響;Effects of Total Sleep Deprivation on Nociceptive Response and Spinal c-fos Expression in Rats
Authors:	蘇宏泰;Hung-Tai Su
Contributors:	中國醫藥大學：臨床醫學研究所碩士班
Keywords:	睡眠剝奪;大白鼠;傷害感受;福馬林測試;c-fos 細胞致癌基因;Sleep deprivation;Rats;Nociception;Formalin test;c-fos
Date:	2009-06-30
Issue Date:	2009-08-12 14:23:36 (UTC+8)
Abstract:	背景目前已知睡眠剝奪會影響許多正常的生理變化，如：免疫反應、傷口癒合、體溫及體重變化，其中包括了疼痛感知。睡眠主要包含了兩大部分：快速動眼期（rapid eye movement）及非快速動眼期（non-rapid eye movement），而前人的實驗多著重在快速動眼期睡眠剝奪對生理的影響。研究目的本實驗乃採取前瞻性之單盲隨機設計，以三十六隻250-350公克大白鼠分別來研究全期睡眠剝奪影響傷害感受的機轉。福馬林測試（formalin test）可量化測量長期疼痛刺激的行為反應，故較為近似真實臨床下的疼痛傷害。本實驗之目的在比較睡眠剝奪及允許自由睡眠之大白鼠在皮下注射福馬林後行為反應及脊髓背角c-fos活動表現上的差異性。研究方法本計劃把三十六隻大白鼠隨機分成C1、C2、C3、D1、D2及D3 六組。先讓老鼠適應環境三天，再分別讓D1、D2及D3組大白鼠睡眠剝奪1、2及3天後給予福馬林測試。C1、C2、C3組大白鼠，則在適應期後另加1、2及3天自由睡眠才進行測試。在測試後一小時內記錄大白鼠對福馬林刺激之疼痛行為反應。並在犧牲大白鼠後，記錄脊髓背角c-fos之活動表現。在完成資料蒐集後，分析比較各相關資料。實驗結果 C1、C2、C3、D1、D2及D3 六組之大白鼠，對施打福馬林後，在疼痛行為反應上並無明顯的差異。然而脊髓背角c-fos之活動表現（number of c-fos-like immunoreactive neurons）?j在睡眠剝奪2及3天後較對照組有明顯增加現象。此增加現象遍佈於脊髓背角的Superficial (I-II), Nucleus Proprius (III-IV) 及Neck (V) lamina內。結論全期睡眠剝奪對化學性疼痛刺激臨床上幾無影響，但經48、72小時全期睡眠剝奪後，大白鼠之脊髓背角c-fos之活動表現有明顯增加現象。此一結果說明相較於快速動眼期睡眠剝奪，全期睡眠剝奪對疼痛行為之影響恐較為複雜。 Background Sleep deprivation has been reported to be related with many physiological changes, including compromise immune function, poor wound healing, decrease in body temperature and loss of body weight. Sleep consists of two major parts, rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. Previous studies focus mostly on the interaction of REM sleep deprivation and pain sensitivity; studies on total sleep deprivation were rare. Aim of the Study The aim of this study is to assess the effect of total sleep deviation on the reaction of rats subject to noxious stimuli and to determine the possible mechanism that how total sleep deprivation influences nociception. Materials and Methods Thirty six rats were randomly allocated into six groups—group C1, C2, C3, D1, D2 and D3. Formalin test was applied to Group D1, D2 and D3 rats on the morning of the second, third and forth day after confinement. Group C1, C2, and C3 rats had the test immediately after their adaptation period. Immediately after formalin injection, behavior reaction was recorded for an hour. The rats were sacrificed and c-fos immunoreactivity of the spinal cord was examined. Data were compared and analyzed to see whether behavior reaction and c-fos immunoreactivity of the spinal cord in rats after subcutaneous formalin injection were different between groups. Results For the chemical noxious stimuli, groups of total sleep deprivation of 1, 2 and 3 days and their corresponding control groups do not respond differently to formalin injection. However, c-fos response (numbers of c-fos-like immunoreactive neurons) to formalin injection was significantly greater in 2 and 3 days of total sleep deprivation compared with liberal sleep environment. This increase was observed in the Superficial (I-II), Nucleus Proprius (III-IV) and Neck (V) lamina of the dorsal horn. Conclusion Total sleep deprivation of 48 and 72 hours induces a significant increase in c-fos immuno-reactive neurons in the dorsal horns of rats. However, the pain related behaviors induced by the formalin test do not show a clinical difference between the sleep deprived groups and adequate sleep groups.
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