多模式功能性造影研究中嗎啡類蛋白對傷害覺反應之調停

Abstract

由於大腦對於疼痛機制的調節非常複雜，要能夠了解各個腦區的對於痛覺的調節作用便需要同時得知神經活動於時間和空間上的變化。近幾年來，功能性造影技術大量的應用在痛覺研究中。功能性磁振照影和正子電腦斷層是最常見的非侵入式造影技術。這兩種造影技術可以反應腦血流相關動態變化及分子間作用等相關訊息,以利於我們將結果類推至大腦中神經之活動。然而在疼痛刺激下，腦部產生之自主止痛的調節作用可能會對疼痛訊息產生干預。其中，又以多巴胺及類嗎啡系統在痛覺緩解作用中佔了相當重要的角色。本論文利用氟－18標定去氧葡萄糖正子照影及腦血量權重功能性磁振照影，觀察大鼠痛覺反應下血液動力參數變化和代謝的反應。基於全腦神經代謝活動與特定腦區內生性神經傳導物質所調控的神經血管偶和反應等實驗結果，我們探討在這些功能性訊號中類嗎啡蛋白所扮演的調停角色。藉此，提出利用功能性照影技術時需要注意神經傳遞物質及自體調節現象對於影像訊號的影響。

Due to the complexity of the pain processing in brain, understanding the antinociceptive modulation within brain areas raises a need for simultaneously detecting the spatiotemporal patterns of neuronal activities. In the last decades, arising consciousness of pain using in vivo imaging techniques have dramatically increased. Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) are the most commonly used techniques providing non-invasive, in vivo measurement of the cerebral hemodynamics as well as molecular processes. However, the antinociceptive effect of the autoregulation may shadow the functional signal under nociception. Among all, dopamine and opioid system are considered to play significant roles in pain modulation, in which endogenous opioid peptides potentially act as a positive regulator. This thesis utilizes cerebral blood volume weighted fMRI and 18F-fluorodeoxyglucose microPET to capture nociception induced hemodynamic responses and metabolic features in the rodent brain. Stating from the investigation of the whole brain neuronal activation to the specific cerebral region with neuronal vascular coupling due to endogenous neurotransmitters, the intervention of opioids in the signal of functional imaging was interpreted. The study highlights the awareness of the endogenous neurotransmission and self-regulation interference in in vivo functional studies of pain.