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標題: | 術前局部麻醉劑處理對溶血磷脂鹼所引發之損傷下甘丙胺肽受器及其相關生化因子的影響 Pre-emptive analgesia reduced GalR2 and pain-related proteins expression on LPC induced animal neuropathic pain model |
作者: | Wan-Ting Lin 林琬亭 |
指導教授: | 呂俊宏(June-Horng Lue) |
關鍵字: | 甘丙胺?,甘丙胺?受器,神經損傷,利多卡因,溶血磷脂醯膽鹼,神經病變疼痛, GalR2,lidocaine,LPC,neuropathic pain,allodynia,hyperalgesia, |
出版年 : | 2014 |
學位: | 碩士 |
摘要: | 先前的研究指出神經傳遞物之一的甘丙胺肽 (Galanin)可利用專一性甘丙胺肽類型二受器 (Galanin receptor 2, GalR2)調控周邊神經系統的痛覺傳遞;當神經損傷時,受損神經元會藉由神經發炎、神經自發性放電及痛覺相關因子釋放的方式,引起神經病變疼痛 (neuropathic pain)。但是有關正中神經髓鞘退化剝離後GalR2及其受質數量上的變化仍欠缺直接證據,更遑論它對正中神經損傷後續誘發行為、發炎的影響。因此,本實驗利用溶血磷脂醯膽鹼(lysophosphatidylcholine,LPC)引發神經髓鞘剝離損傷脫落,作為探討神經損探討正中神經以LPC處理後,GalR2與神經病變疼痛的關係。
LPC處理後,實驗動物手術側產生神經病變疼痛的行為反應。以細胞免疫化學法標誌後,發現在正常大白鼠的背根神經節中,GalR2免疫反應神經元的數量相當少,且主要為小型神經元;在LPC處理一週後,GalR2免疫反應神經元佔背根神經節的的百分比明顯上升,而且在體型的分布有擴展至中型神經元,且相較於小型神經元在數量上有明顯較多的現象。配合雙重免疫螢光標誌法染色時,發現神經損傷後一週GalR2與辣椒素受器 (VR1)、P2X3、peripherin、NF200、NPY及MMP9等的雙重標誌神經元數目及占背根神經節中的比例都有顯著上升。 鑑於神經病變疼痛成因之一有可能來自於神經末端自發性放電 (sponteous discharge),本實驗又利用抑制鈉離子通道之局部麻醉劑-利多卡因 (lidocaine)術前處理;結果發現lidocaine術前處理可減緩LPC誘發實驗動物神經病變疼痛程度,並降低神經損傷之背根神經節中GalR2免疫反應神經元數量及百分比上升幅度。配合雙重免疫標誌染色,同時也發現神經損傷後一週GalR2與辣椒素受器 (VR1)、P2X3、peripherin、NF200、NPY及MMP9等的雙重標誌神經元數目及占背根神經節中的百分比也有緩和其上升的幅度。 除此之外,LPC處理一週後楔狀神經節內GalR2免疫反應神經元的數量也會高於正常組別,並因為lidocaine處理而有下降的現象。由結果顯示lidocaine的處理可造成神經過敏痛及痛覺相關化學因子的改變,進一步引發抑制痛覺表現的結果。 Previous studies have shown that Galanin modulated peripheral pain sensation via galanin receptor type 2 (GalR2). Following nerve injury, inflammation, spontaneous discharge and upregulation of pain related factors would involve in neuropathic pain development. To our knowledge, the correlation between median nerve demyelination and GalR2 and its substrate expression levels has not been documented; and yet the effect of GalR2 on medain neuropathic pain is not valid. Thus, using LPC treated median nerve injury model, we investigate the role of GalR2 and its pain corelated factors in the upper limb neuropathic pain. One week after LPC treatment of median nerve induced mechnical allodynia and thermal hyperalgesia. Immunohistochemistry analysis showed that GalR2-like immunoreactive (-LI) neurons were predominately in small-size DRG neurons of normal rats. However, one week after LPC treatment, GalR2-LI neurons not only increased in its percentage but also distributed in medium- and large-sized neurons. Moreover, to characterize GalR2-LI neurons in the DRG was using immunofluorescence double labeling for NF200, peripherin, pain-related factors including vanilloid receptor subtype 1 (VR1), P2X3, NPY, nNOS, Galanin, or MMP9. We found that the number and percentage of GalR2-LI neurons colocalized with NF200, P2X3, NPY, nNOS, Galanin and MMP9 were increased in the LPC-treated DRG. Furthermore, lidocaine pretreatment attenuated the number of upregulated GalR2-LI neurons in the LPC-treated DRG. Our study also found that one week afterLPC treatment, the number of GalR2-LI neurons in the cuneate nucleus of LPC treated rats was higer than that in the control group. The present results suggest that lidocaine pretreatment relieved the development of neuropathic pain partially pass through reducing GalR2 expression. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/56065 |
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顯示於系所單位: | 解剖學暨細胞生物學科所 |
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