| 摘要: | 退化性關節炎被認為是最盛行的關節疾病之一。其表現以關節軟骨退化, 關節間隙變窄,產生骨刺為主。退化性關節炎容易侵犯膝關節,而且是造成膝 關節疼痛之主因。當前對退化性關節炎之病生理機轉已有廣泛的研究,但針對 造成關節疼痛之危險因子與分子機轉目前尚未透澈。本研究首先以患有膝退化 性關節炎、需要接受膝關節置換手術之病患為研究對象,以病歷回溯方式研究 分析嚴重膝關節痛的危險因子。然後再選取需要進行手術之膝退化性關節炎之 病人,在手術中抽取其膝關節液進行發炎疼痛因子分析,以證實發炎疼痛因子 在分子機轉路徑扮演之角色。本研究結果顯示,Body mass index (BMI)平均值較 低之病人(BMI 少於 25、BMI 介於 25 至 30、BMI 介於 30 至 35),相較於 BMI >35 的病人,嚴重疼痛危險比分別為 19.69、14.80 和 11.44。X 光膝關節影像分 級,根據 Kellgren-Lawrence (K/L) classification,K/L grade 3 相較於 K/L grade 2 發生嚴重疼痛之危險比為 0.43。腎功能不全之病人相較於腎功能正常之病人的 嚴重疼痛危險比為 2.96。針對疼痛之分子路徑分析中,在病人之關節液內有發 現 PGE2 釋放,但偵測 ATP 只有很低的濃度;另外也在關節液中發現 COX-2 的 蛋白質,卻沒有 COX-1 的蛋白質。在分析退化性關節炎病人的關節液內發現有 COX-2 與 PGE2 的表現,說明 PGE2 能造成關節之軟骨破壞和產生疼痛。在分析 嚴重疼痛度的危險因子中發現,腎功能不全是其中一個危險因子。退化性關節 炎的病人,普遍是老年人,在臨床上照顧患者之關節疼痛時,亦須注意病人合 併其他之系統性疾病的可能。在目前治療疼痛之藥物,仍以 COX-2 抑制劑為最 常用,所以在治療上需注意藥物引起之腎臟毒性。除了 PGE2 造成疼痛之路徑外,
亦希望可以找出其他引起關節疼痛之新路徑,以作為開發新藥治療之依據。
Osteoarthritis (OA) is considered to be the most common arthritis in the world. Clinical manifestation of osteoarthritis includes degradation of articular cartilage, joint space narrowing and osteophytes formation. OA commonly affects knee joints, and it is a main cause of knee joint pain. Nowadays, pathophysiology of osteoarthritis has been well studied. However, risk factors and molecular mechanism of osteoarthritis-induced pain is not well known now, so the objective of this study is to investigate what risk factors and molecular mechanism how to affect osteoarthritis-induced pain. This was a retrospective study; target population in this study was patients suffering from osteoarthritis, who were suggested to receive total knee replacement surgery, from January 2007 to December 2012. The results revealed that body mass index (BMI) of OA patients (BMI less than 25, BMI between 25 and 30, BMI between 30 to 35), compared to at BMI> 35 patients, odds ratio of developing severe OA-induced pain was 19.69, 14.80 and 11.44 respectively. According to Kellgren-Lawrence (K/L) classification, OA patients with K/L grade 3 compared to that with K/L grade 2, odds ratio of developing severe pain is 0.43. Odds ratio of developing severe OA-induced pain in patients with renal insufficiency is 2.96, compared to patients with normal renal function. To investigate molecular pathway of OA-induced pain, luminescence assay was used for detecting ATP concentration in synovial fluid; however, no ATP was detected in all samples. Next, we checked PGE2 concentration in synovial fluid by ELISA, PGE2 was detectable.
By western blot analysis, COX-2, not COX-1 protein expression was revealed in
synovial fluid. In this study, COX-2 protein and PGE2 was detected in synovial fluid of OA patients, similar to other previous study. We can suggest that PGE2 is a main mediator to degrade cartilage and cause pain. Besides, analysis of risk factors of severe OA pain, renal insufficiency is found as a risk factor. In clinical practice, many elderly patients suffer from knee osteoarthritis, we must pay attention that elderly patients also suffer from other comorbridities. Because of persistent joint pain, analgesic drugs especially selective COX-2 inhibitors are prescribed to patients. However, one of side effects of this drug is renal toxicity. We must keep in mind to check renal function of patient after a period of therapy. Besides the pathway of PGE2 causing OA-induced knee pain, we also want to explore other novel mechanism of OA-induced pain because new drugs can be developed according to novel pathway of pain. |
