神經細胞死亡或軸突不適當的生長都可能是神經病變性疼痛發病的原因，神經膠細胞遞送神經滋養因子(GDNF)在保護受損後的感覺神經元提供一種有潛力的治療方式來治療難纏的疼痛。然而，連續給予中樞神經滋養因子是太過昂貴和持續上有困難。因此，我們評估傳送GDNF基因來治療神經病變性疼痛的潛力。重組腺病毒附加GDNF基因的特性表現在提高培養神經元細胞的生存能力。在使用單一椎管注射Ad-GDNF後能夠提高脊椎內GDNF的量至少四個星期，並能改善大鼠坐骨神經軸索切所引起的神經病變性疼痛持續時間。不過，大鼠在接受椎管注射Ad-GDNF治療後的最初兩個星期卻出現痛覺過敏的現象。免疫螢光分析證實了GDNF降低了神經受損後的神經元減少。令人意外的是，部分Ad-GDNF治療後的老鼠，出現了不同程度的毛髮喪失。作組織學切片檢查分析，證實Ad-GDNF治療組老鼠皮膚毛髮脫落導致於嚴重的毛囊退化。總而言之，這個實驗說明了傳送GDNF基因在改善慢性疼痛的優點和可能發生的負面影響。

Neuronal cell death may be responsible for the pathogenesis of neuropathic pain. Glial cell line-derived neurotrophic factor (GDNF) protects sensory neurons after injury and offers a promising alternative for the management of intractable pain. However, continuous administration of trophic factors into the central nervous system is costly and difficult to maintain. Therefore, we evaluated the potential of intrathecal GDNF gene delivery for the treatment of neuropathic pain. Recombinant adenovirus encoding GDNF (Ad-GDNF) was characterized and shown to enhance viability of neuronal cultures. After intrathecal injection of Ad-GDNF, an elevated GDNF level was observed in spinal cord for four weeks. In rats with sciatic nerve axotomy,intrathecal injection of Ad-GDNF significantly ameliorated the duration of neuropathic pain. However, animals treated with Ad-GDNF developed hyperalgesia in the early stage of treatment. Immunofluorescence analysis indicated that intrathecal GDNF gene delivery prominently attenuated the neuronal loss due to nerve injury. Unexpectedly, varying degrees of hair loss was found in some rats receiving Ad-GDNF. Histological analysis revealed that hair loss resulted from severe degeneration of hair follicles in skin from Ad-GDNF-treated animals. In summary, the present study demonstrate the feasibility and limitations of GDNF gene delivery for the management of neuropathic pain.

Abstract……………………………………………………2.
摘要…………………………………………………………3.
引言…………………………………………………………5.
材料與方法…………………………………………………8.
結果…………………………………………………………16
Figure 1(a)………………………………………………28.
Figure 1(b)………………………………………………29.
Figure 1(c)………………………………………………30.
Figure 2……………………………………………………31.
Figure 3……………………………………………………32.
Figure 4……………………………………………………33.
Figure 5……………………………………………………34.
Figure 6……………………………………………………35.
Figure 7……………………………………………………36.
Figure 8……………………………………………………37.
討論……………………………………………………………23.
結論……………………………………………………………27.
References……………………………………………………43.

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