中風後中樞神經疼痛是指中風後中樞神經系統受損或異常,導致疼痛的一種症狀,由於診斷上有其困難性,在機制上目前仍不清楚,因而在治療方面受到了侷限。本研究將針對早期發覺與診斷,以及治療法,這兩個議題來進行研究。研究目的為:A.找尋中風後神經疼痛的早期診斷生物指標,包括神經生長因子(BDNF)、P2X受體、cytokines等蛋白表現以及腦波(EEG)的量測。目前沒有標準化的可接受的診斷標準,使我們能夠準確區分中風後中樞神經疼痛類型。制定更客觀的方法來提供明確的診斷至關重要。B.發展中風後中樞神經疼痛新治療法:研究非侵入性腦刺激機制,經顱直電流刺激術(tDCS),光學遺傳學(optogenetic)刺激參數研究,光學遺傳學以及化學遺傳學(chemogenetic)新治療法研究,做為未來中風後中樞神經疼痛治療的應用。本研究將檢測六種演算法,配合穿戴式遠端回饋控制設備,來監控特定腦核區神經細胞的狀態,達到早期發覺與偵測的目的。並且透過此腦波EEG回饋訊號的偵測,給予病人最佳化的tDCS或是光學遺傳學的刺激,以此興奮或抑制相關腦核區的神經細胞,以達到治療效果。本研究計畫將是跨領域研究,其中包括基礎與臨床醫學的整合,動物模式與臨床模式的結合,並且跨越基礎研究、工程數理資訊、臨床醫學三部分,本研究將會帶來實質性診斷和治療的意義,屬於前瞻性的轉譯研究計畫。
"Stroke is a leading cause of death and disability in industrialized countries. Central post-stroke pain (CPSP) refers to pain that results from a primary lesion or dysfunction of the central nervous system after a stroke. Because of potential under-diagnosis, difficulty managing the condition, and studies that have been unable to clearly establish the detailed mechanisms of CPSP, diagnostic and therapeutic strategies for CPSP are limited. There are two urgent issues, diagnosis and treatment, that are encountered when facing CPSP. There are currently no standardized accepted diagnostic criteria, clear definitions or simple diagnostic tests that enable us to accurately distinguish between pain types. Developing more objective approaches to providing a clear diagnosis is essential. Current treatments for CPSP involve pharmacological approaches that are not very effective in achieving a satisfactory therapeutic response. Non-invasive brain stimulation, such as tDCS, has been developed for this purpose. Based on our findings of the involvement of P2X receptors, BDNF, and cytokines in CPSP and abnormal neuronal hyperexcitability, our first hypothesis is that these factors are valuable predictive elements for the occurrence of central pain conditions. Current efforts in developing treatments for CPSP have focused on regulating the sensitized thalamocortical pathway. To achieve specific and efficient effects on the regulation of hyperexcitable neurons, we need to develop methods that specifically target these neurons and produce a suppressive effect. Our second hypothesis is that targeting the hyperexcitability of the damaged thalamocortical system is a rationale for further studies on therapeutic agents for the treatment of central pain, including the use of non-invasive brain stimulation techniques, such as tDCS. Thus, the use of pre-clinic experimental models which will contribute aids in addressing these issues serves as an important basis that hence may be translated into the clinical setting to benefit patients.
The general aim of the present proposal is to address the current difficulties in the diagnosis and treatment of CPSP. We propose two specific aims to achieve this important goal. Specific Aim I focuses on searching for a biomarker for the early detection and diagnosis of CPSP. The biomarkers include brain-derived neurotrophic factor (BDNF), P2X receptors, and cytokines and the application of analytic technique of electroencephalography (EEG). Specific Aim II focuses on developing a therapeutic strategy for the treatment of CPSP. We will investigate the neuronal mechanisms that underlie non-invasive brain stimulation techniques: transcranial direct-current stimulation (tDCS). We will develop optimal stimulation parameters for clinical application. We also propose to investigate the therapeutic effect of novel optogenetic and chemogenetic approaches to provide effective treatment options for CPSP in patients. A novel, wearable, remote feedback-controlled device will be constructed based on EEG signal detection and analysis. We will establish sophisticated animal models mimicking human neurological disorders and handle wide varieties of approaches such as molecular biology, biochemistry, behavioral assessments and neuro-pharmacological, electrophysiological methods to bring integrated dynamic links from the hemorrhagic stroke pre-clinical mouse models to human diseases. The proposed study will be multidisciplinary translational research, combining basic and clinical applications in animal disease models and clinical patient experiments."