2012-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/660098摘要：周圍神經病變患者經常有兩種看似矛盾的臨床表現：(1) 皮膚感覺靈敏度減少與 (2)神經性疼痛。過去幾年我們已成立了小片皮膚切片系統研究小直徑神經末梢，在糖尿病患者的皮膚，表皮神經密度 (intraepidermal nerve fiber density，IENF density) 有明顯降低，這一病理現象是小纖維神經病變的診斷根據。但是皮膚神經的支配減少，反而造成神經性疼痛的機制仍然不清楚。無論是周邊敏感 (peripheral sensitization) 和中樞可塑性，都可以造成神經退化後之神經痛。然而這個問題，一向缺少系統性的研究。本研究將探討於糖尿病神經病變所致神經痛於皮膚神經末梢和大腦的生物標誌(biomarkers)。於皮膚，我們將以免疫化學染色與生化分析探討神經營養因子和發炎分子與神經痛的相關性。於中樞可塑性，我們將以神經影像和生理探討皮膚神經退化後的大腦變化，包括大腦功能和結構的連結 (functional and structural connectivity)，這些定量的影像數據將一起與表皮神經纖維密度比較分析，以了解中樞過敏化 (central sensitization) 的程度。預期這一研究成果將可以對皮膚神經退化所致之神經性疼痛的病理生理學提供全面性的資訊，作為轉譯醫學與個人化醫療的基礎。<br> Abstract: Patients with peripheral neuropathy frequently have paradoxical manifestations of reducedsensations and neuropathic pain. We have set up skin biopsy system to examinesmall-diameter nerve terminals in the skin and diabetic patients have a high prevalence ofreduced intraepidermal nerve fiber (IENF) density, i.e. small fiber neuropathy. Themechanisms of neuropathic pain under such a status of reduced innervation remain elusive.Both peripheral sensitization and central plasticity can contribute to the maintenance ofchronic neuropathic pain after skin nerve degeneration. This issue, however, has not yetsystematically studied.This proposal will examine the biomarkers of pain at skin nerve terminals and the brain.We will investigate molecular natures of peripheral sensitization in the skin withimmunohistochemsitry and reverse transcriptase-polymerase chain reaction on neurotrophins,excitatory molecules, and proinflammatory molecules. The expression of these moleculeswill be normalized to IENF density, which may reflect the degree of peripheral sensitization.In the central plasticity, we will employ functional imagaing and physiology to explorecerebral plasticity after skin nerve degeneration. We hypothesize that both functional andstructural connectivity will be altered in neuropathic pain after nerve terminal degeneration.These quantitative imaging data will be analyzed together with IENF density to understandthe degree of central sensitization. The cortical plasticity in small fiber neuropathy will beassessed and modulated with transcranial magnetic stimulation.The results of the current proposal will provide comprehensive information underlyingpathophysiology of neuropathic pain due to skin nerve degeneration.皮膚神經周邊神經病變糖尿病功能性磁振造影神經影像Skin innervationNeuropathic painFunctional imagingDiabetic neuropathyNeuroimaging