2012-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/686948摘要：疼痛是巴金森氏病患者常見的非運動方面的症狀，有一些患者在確診前就會出現局部肢體僵硬疼痛，且隨著病程而加劇。在疾病後期時，多巴胺藥物治療所引起之藥物波動與動作異常也與疼痛有關，進而影響生活品質。在西方國家的研究，疼痛在巴金森氏病的盛行率為60-80%，在台灣或其他亞洲國家則鮮有報告。巴金森氏病患者產生疼痛的機轉並不清楚。最近研究指出紋狀體與邊緣系統的基底核在感受到痛之前即扮演非常重要的角色。當病患體內左多巴缺乏時會導致腦部皮質─紋狀體之訊號異常增加、促進感覺的表現且造成感覺皮質的大量被活化，進而引起疼痛。功能性磁振造影（fMRI）的研究顯示纖維肌痛症和慢性疼痛和體位皮質、視丘以及基底核的活化有關，巴金森氏病的疼痛究竟是和腦部哪些部位的活性有關， 值得探討。此外，近來亦有研究顯示DRD2、DRD3及COMT三種基因多型性與慢性疼痛有關，但是否與巴金森氏病之疼痛有其相關性，則尚待研究。巴金森氏病患者的疼痛有時候是相當難治療，甚而比運動功能的異常更加影響生活品質。 近年來重複經顱磁刺激術（rTMS）已被證明能藉由調節神經活動，有效治療慢性疼痛。若病人本身是藥物難治型憂鬱症，又伴有疼痛的患者，給予高頻（10 赫茲）之經顱磁刺激術（rTMS），可將此刺激傳送至左邊背側前額葉皮質（DLPFC），已被證明可減少病人的疼痛，但可能無關其憂鬱症。重覆腦部磁脈衝波之治療已被美國食品衛生管理局核准用於憂鬱症的治療，其安全性已被接受。因此，值得探討經顱磁刺激術是否可以有效地改善巴病患者的這些無法以鎮痛劑和類多巴胺治劑治療的頑固型疼痛症狀。基於上述，本計畫將對於巴金森氏病患者的疼痛做深入的研究。主要的研究目標分為下面幾點：（1） 瞭解台灣地區巴金森病患者之疼痛症狀的盛行率以因疼痛造成之生活品質影響（2） 藉由全民健康保險資料的串連檔案，比較各種相關環境危險因子的暴露以及肢體長期疼痛與否對巴病發生的危險性的影響，藉以證明疼痛是否為導致巴病的危險前驅症狀（3） 利用功能性磁振造影研究巴金森氏病的疼痛究竟是和腦部哪些部位的活性有關（4） 分析疼痛的發生以及程度是否與DRD2 Taq1A alleles、DRD3 S9G 及COMTVal108/158Met polymorphism 相關（5） 探討經顱磁刺激術是否可以有效地改善巴病患者的這些無法以鎮痛劑和類多巴胺治劑治療的頑固型疼痛症狀<br> Abstract: Pain has been recognized as an important and distressed non-motor symptom ofParkinson’s disease. Patients with advanced PD, pain syndrome is often related with motorfluctuations and dyskinedia induced by dopaminergic treatment and causes significantimpairment of life quality. Five different types of pain have been described in PD patients: (1)a musculoskeletal pain (2) radicular and neuritic pain (3) pain associated with dystonia (4)discomfort due to akathisia and (5) central pain syndromes. Although recent study showedthat the prevalence of pain syndrome in PD is approximately 60-80 % in western countries,few studies have been reported in Taiwan and other Asian populations. It is also unknownwith the association of pain and quality of life in PD.The pathophysiology of pain perception in PD is not well understood. Basal gangliamay act as an important gating role for nociceptive information within the striatum and limbicsystem before it reaches consciousness. By using functional MRI, the threshold of painsensation and the activation area have been demonstrated in fibromyalgia and chronicheadache. These included somatosensory cortex, thalamus and basal ganglia. It is uncertainthat which areas may be involved in PD patients with the various pain syndrome.Meanwhile, the genetic polymorphism of dopamine D2 and D3 transporters, andcatechol-O-methyltransferase have been found to be associated with pain tolerance inchronic pain, it is not known whether these types of polymorphism are related to painsyndrome in PD.The management of pain syndrome in PD is critical to improve life of quality. Repetitivetranscranial magnetic stimulation (rTMS) has been shown to be effective in treating chronicpain by modulating neural activities. It is worthwhile to investigate whether rTMS stimulationof the left is effective to improve pain syndrome in PD which are not responsive to analgesiaand optimal levodopa therapy.Based on the aforementioned background on the current research on Pain symptoms inPD, we propose this 3 years proposal with 5 aims including:1. To examine the prevalence of pain in PD patients and their life quality, including pain types,the intensity and the duration of pain, in a large cohort of PD2. To evaluate the relation between preceding pain symptoms and risk of PD in a nationwideprospective cohort in Taiwan3. To study the change of pain threshold and the activated brain area responding to pain in PDby functional MRI4. To investigate the association of pain in PD patients with the genetic polymorphism ofDRD2 Taq1A alleles, DRD3 S9G and COMT Val108/158Met5. To study the effect of left dorsolateral prefrontal rTMS on pain relief in PD patients.巴金森氏病疼痛DRD2DRD3COMT 基因多型性重覆腦部磁脈衝波 功能性磁振造影Parkinson’s diseasepainDRD2DRD3COMT polymorphismfMRITMS