ASIC3或TRPV1基因剔除會減緩單關節炎 誘發的機械性痛覺敏感現象

自體免疫疾病是一個慢性的情況，起始於自體抗原的免疫功能喪失代表異質的雜亂，而去攻擊特定器官或是多種器官系統。類風溼性關節炎是一種慢性、漸進式、全身性的、特徵是關節滑膜結締組織嚴重破壞的發炎疾病。類風溼性關節炎主要涉及組織的發炎，而不是關節退變。雖然發炎會造成類風濕性關節炎病患的疼痛，但這並不是唯一造成疼痛的原因。有些病患使用抗發炎疾病修飾抗風濕性藥物治療並不能改善疼痛的情況。關節發炎通常伴隨著組織酸化。因此，酸敏感接受器對於類風溼性關節炎可能扮演關鍵角色。使用兩種基因剃除(ASIC3和TRPV1)的小鼠來研究類風溼性關節炎。每周在關節注射一次5µg CFA，連續四周，用以建立模擬類風溼性關節炎小鼠的動物模式。模擬期間測量關節寬度和關節組織病理變化，以監測關節炎的過程。以Von Frey尼龍絲來評估注射CFA後小鼠的疼痛行為反應。在野生型和基因剔除的小鼠關節注射CFA會誘發二級機械性痛覺敏感現象。ASIC3和TRPV1基因剔除的小鼠可以減緩類風溼性關節炎在後期的機械性痛覺敏感現象。

關鍵字

關節炎

並列摘要

Autoimmune diseases (ADs) are chronic conditions initiated by the loss of immunological tolerance to self-antigens and represent a heterogeneous group of disorders that afflict specific target organs or multiple organ systems. Rheumatoid arthritis (RA), one of ADs, can be defined as a chronic, progressive, systemic, inflammatory disease of connective tissues characterized by the severe destruction in synovial joints. RA involves primary tissue inflammation rather than joint degeneration. Although inflammation contributes to pain in RA, however, it may not be the only factor. For some patients, pain is not improved despite of the treatment with anti-inflammatory disease-modifying anti-rheumatic drugs. The aim of this thesis is to identify novel genes that are involved in RA-induced pain. Given that joint inflammation is usually accompanied by tissue acidosis, proton-sensing receptors could be the candidates for RA. Two knockout mice (ASIC3-/- & TRPV1-/-) were generated for the RA study. After intra-articular injection into a stifle joint with complete Freund’s adjuvant (CFA) once per week for 4 weeks, long-term mechanical hyperalgesia was developed in wildtype and knockout mice. Both of ASIC3-/- & TRPV1-/- reduced RA-induced mechanical hyperalgesia in the late phase.

並列關鍵字

arthritis

參考文獻

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ASIC3或TRPV1基因剔除會減緩單關節炎誘發的機械性痛覺敏感現象

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