疼痛是臨床的最常見症狀之一，也是很多疾病的重要標誌。有效緩解疼痛是臨床治療的重要目的。中醫對疼痛治療有豐富的經驗，中醫學中很多外感和內傷雜病都以疼痛為早發症狀。 有關疼痛辨治值得學習的文獻很多，但從分類辨治的角度時常出現有辨無治，有治無辨的情況。不經過大量的文獻閱讀難以滿足所有臨床需要。 本文從辨治結合的角度，通過多層次多角度總結不同中醫理論來探討的疼痛辨治，希望能夠有助於更準確地判斷病情以及有的放矢的針對性治療，爲更好地認識和掌握疼痛做一點探索。 採用文獻檢索的方式搜集相關文獻。以計算機爲工具，應用WindowsOffice套件等軟件，收集古代經典及近現代中醫疼痛辨治相關文獻。 資料來源主要包括： 中國期刊全文數據庫 香港浸會大學圖書館醫學專著 以中醫辨治疼痛爲主要線索，檢索項綜合了以下檢索途徑：題名、作者、主題、關鍵詞。 搜索“疼痛”、“中醫”、“辨治”、“研究”、“分類”等關鍵詞。 檢索出136篇近現代中醫疼痛辨治方面文獻，並參考相關古典文獻、當代中醫教材等。 在此基礎上適當整理，分類歸納辨治方法的理論及應用病案。分別從辯因、辨機、辨位、辨經、辨病、辨時、辨方、辨藥、辯性等九方面歸納總結，概括爲以辨論治的內容共九類，有辨無治的內容一類以及綜合應用一類。因辨論治，在臨床上隨症應變，以不同組合綜合應用居多。治療方法有應用中藥、方劑、外敷、鍼灸、推拿以及近代常用技術電針、埋線等。 通過對辨治結合的研究歸納，以及對疼痛辨治更注重邏輯性的分類論述，清晰展示現有的疼痛理論研究概況。 關鍵詞：疼痛，辨治，分類，綜述。

京都大学 / 新制・課程博士 / 博士(薬学) / 甲第23847号 / 薬博第854号 / 新制||薬||242(附属図書館) / 京都大学大学院薬学研究科薬学専攻 / (主査)教授 金子 周司, 教授 土居 雅夫, 教授 竹島 浩 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

(調査・統計)

在本實驗室之前的研究中顯示在發炎狀態的大白鼠上以intrathecal (i.t.) 方式給予angiotensin IV (Ang IV) ，Ang IV 是insulin-regulated aminopeptidase (IRAP) inhibitor，可以減少腳掌發炎之大白鼠的疼痛過敏化。然而，這個由Ang IV所產生之效果背後的機制還未被完全釐清。 在這次的實驗中，我們利用由carrageenan引起腳掌腫脹之大鼠進行plantar test來研究Ang IV所產生之抗疼痛過敏化其中可能機制。由於有文獻指出，在發炎狀態的大白鼠上以intrathecal (i.t.) 方式給予oxytocin可產生一劑量相關性的抗疼痛過敏化作用，因此我們推測在大白鼠的脊髓層次上由oxytocin以及Ang IV所個別誘導的抗疼痛過敏化之間可能有關聯性。利用 i.t.單獨給予atosiban (selective oxytocin receptor antagonist) 可以觀察到一個較強烈的疼痛過敏化現象，然而合併給予atosiban，可使Ang IV所產生的抗疼痛過敏化完全被阻斷掉。因此我們推測oxytocin在以intrathecal (i.t.) 方式給予Ang IV而阻斷IRAP的活性，進而產生抗疼痛過敏化作用的過程中是一個主要的IRAP受質。 當我們在carrageenan誘導疼痛過敏化的大白鼠上單獨給予低劑量之oxytocin並沒有產生統計上顯著之抗疼痛過敏作用。然而合併給予oxytocin和Ang IV後，則可以有觀察到Ang IV 能增加並且延長oxytocin所引起的抗疼痛過敏化作用。 就內生性oxytocin來看，電刺激paraventricular hypothalamic nucleus (PVN)已被證實可以增加內生性的oxytocin分泌到脊髓。而這樣的一個神經路徑被發現和疼痛的調節具有很密切的關聯性。從我們的結果中，我們發現在carrageenan誘導疼痛過敏化的大白鼠上，i.t.給予Ang IV可以延長PVN電刺激產生的抗疼痛過敏化作用，由此推測 Ang IV可能可以保護內生性oxytocin不被分解或失去活性。 除了oxytocin之外，IRAP在體外的實驗中被證實可以分解數種具生理活性之peptides 的N-terminal amino acid，其中包括vasopressin, bradykinin 以及 enkephalin等。在這些物質中，bradykinin已被證實在週邊發炎的過程中具有重要的調控效果，若IRAP在週邊組織扮演了一個分解促發炎物質的角色，利用Ang IV也許可以去阻斷IRAP之活性進而增加這些促發炎物質。因此，我們在由carrageenan誘導疼痛過敏化的動物模式上利用腳掌局部注射 Ang IV來探討在發炎部位Ang IV可能的作用。我們猜測Ang IV 可能可以調控不同物質(例如：bradykinin)而在發炎部位產生局部之作用， 但結果顯示在疼痛過敏化以及腫脹程度上，Ang IV並不具有調控週邊組織發炎過程的能力。所以推測Ang IV在週邊發炎位置可能並沒有扮演非常重要的角色。 總而言之，本實驗結果證實了Ang IV以及 oxytocin在發炎大白鼠的脊髓層次上所個別引起之抗疼痛過敏化作用之間具有相關性，其中的機制可能是Ang IV在發炎大白鼠的脊髓層次上藉由抑制IRAP降解oxytocin的活性，進而產生抗疼痛過敏化的效果。 / In our previous study, we showed that intrathecal (i.t.) administration of angiotensin IV (Ang IV), an insulin-regulated aminopeptidase (IRAP) inhibitor, could attenuate hyperalgesia in rats with inflammation. However, the underlying mechanism(s) for this effect of Ang IV was not clarified yet. Using the plantar test in rats with carrageenan-induced paw inflammation, we attempted to investigate the possible mechanism(s) of Ang IV in the present study. Because it has been reported that i.t. administration of oxytocin produced a dose-dependent anti-hyperalgesia effect in rats with inflammation, we speculate that there is a possible correlation between the oxytocin-induced and angiotensin IV-induced anti-hyperalgesia at the spinal level in rats. Using i.t. co-administered atosiban (a selective oxytocin receptor antagonist), the anti-hyperalgesia effect of Ang IV was completely abolished, although a severer hyperalgesia was observed in rats receiving atosiban alone. This indicates that oxytocin could be the major substrate of IRAP responsible for the anti-hyperalgesia caused by intrathecal administration of Ang IV, which blocked the activity of IRAP. Using i.t. administration of oxytocin in rats with carrageenan-induced hyperalgesia, the anti-hyperalgesia effect of oxytocin was potent and significant. When Ang IV was co-administered with the low dose of oxytocin, a significant enhancing effect of Ang IV on anti-hyperalgesia of oxytocin was observed. In view of the endogenous oxytocin, electrical stimulation of the paraventricular hypothalamic nucleus (PVN) has been proved to cause the increase of oxytocin release at the spinal cord. This neural pathway has been found to be highly related to the modulation of pain. In our results, we found that i.t. administration of Ang IV could prolong the anti-hyperalgesia induced by PVN stimulation. This suggests a possible protective effect of Ang IV on endogenous oxytocin degradation/dysfunctioning. In addition to oxytocin, it was well known that IRAP is able to cleave the N-terminal amino acid from several bioactive peptides in vitro, including vasopressin, bradykinin and enkephalin. Among these substrates, bradykinin has been demonstrated to be an important mediator in peripheral inflammation. It is a pro-inflammatory substance that can be enhanced by Ang IV, if the peripheral IRAP plays a role in its degradation. Therefore, we examined the possible local effect of intraplantarly injected Ang IV on the carrageenan-induced hyperalgesia in the same model. However, our results showed no effect of local Ang IV on hyperalgesia and paw edema, indicating that Ang IV may not be able to regulate the peripheral inflammatory process. Overall, the present study verified the possible interaction between the oxytocin-induced and angiotensin IV-induced anti-hyperalgesia at the spinal level in rats with inflammation. It suggests that Ang IV may act though the inhibition of the activity of IRAP to reduce the degradation of oxytocin, thereby lead to anti-hyperalgesia in rats with inflammation.

(物理療法)

本論文の目的は，Acceptance & Commitment Therapy (ACT) に含まれる価値の明確化の手続きが，身体的な痛みを抱える者の行動を活性化させるかどうかを検討することであった。その結果，基礎研究（研究1, 2）からは，自らの過去の行動の機能を記述することにより，特定の課題の遂行量や時間が増加することが示された。また，臨床研究（研究3, 4）からは，価値の明確化を含むACTにより，慢性疼痛患者の価値に基づく活動や日中活動量が増加することが示された。 / 博士(心理学) / Doctor of Philosophy in Psychology / 同志社大学 / Doshisha University

University of Macau / Institute of Chinese Medical Sciences

以身體知覺作為出發點，將疼痛經驗帶入虛擬影像中，藉此探討身體知覺的運作及兩者間的關聯性，蒐集相關文獻資料與實際作品的分析，深入瞭解如何在虛擬世界透過身體知覺建立自我存在，最後，以創作行動去探討虛擬影像與身體知覺，並以展覽的方式，藉由作品與人之間的互動，提供進一步的思考。 透過文獻資料的彙整瞭解關於身體知覺的形成、記憶經驗、身體知覺與「我的身體」、影像的演進、虛擬影像等加以蒐集與彙整，從中得知，進以瞭解虛擬影像中身體知覺的鍵結。接下來，透過相關案例的分析，與理論相互驗證，讓自己在創作的脈絡和歷程有更清楚的思維。最後，整理出自己對身體知覺及虛擬影像的觀點，進而執行下一階段的創作行動。 本研究以創作方式探討「身體知覺－虛擬影像」，透過擴增實境藝術的創作行動，期許觀者在體驗作品時，能透過虛擬影像，喚起個人的身體知覺的運作，進而引導觀者對虛擬與現實間的「自我存有」有更大的想像與討論。 / The motivation of this study is, by combining the pain experience with the virtual images, to explore the association among operations of physical consciousness, pain experiences and synthesized virtual images. The ways to use physical consciousness when building self-existence in virtual images are investigated by collecting relevant literature and performing analysis of empirical works. Finally, the overall concepts are implemented and realized in the form of an exhibition which facilitates the reflections of visitors after interacting with these virtual images provided in the exhibition. The overall research activity begins by compiling the pieces of literature. Specifically, to understand, collect, and aggregate the concepts of physical consciousness and its relationship with "My Body," memorable experience, image evolution, and virtual images. Next, via the analysis of the related cases and the mutual verification of the theories, the contexts and thinking of the process of artifact creation are clarified. Lastly, this research systematizes a unique and novel view of physical consciousness and virtual Images, which is helpful for the design activity in the next stage. Consequently, the main focus of this study is to explore the concepts of physical consciousness of virtual images in a novel way. By amplification of augmented reality art, it is anticipated that the audiences evoke physical consciousness operations of themselves in the exhibition and that the research results enable bigger imagination and discussion with virtual and reality “Self-existence.”

京都大学 / 0048 / 新制・課程博士 / 博士(薬学) / 甲第20320号 / 薬博第830号 / 新制||薬||240(附属図書館) / 京都大学大学院薬学研究科薬学専攻 / (主査)教授 金子 周司, 教授 髙倉 喜信, 教授 山下 富義 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

憂鬱症是盛行的精神疾病之一。慢性疼痛或是處在長期壓力情境的患者常與憂鬱症產生共病。在動物研究中，類鴉片delta受體制效劑能產生抗憂鬱效果，並且在發炎性疼痛的研究也指出類鴉片delta受體制效劑能展現抗痛覺過敏的效果。本研究主要利用大白鼠腦室內給予類鴉片delta受體制效劑SNC80以及三環抗憂鬱劑amitriptyline，來探討並比較其所產生的抗憂鬱效果在發炎性疼痛或長期壓力情境下與正常情境下的異同。大白鼠強迫游泳試驗被用來比較測試藥物的抗憂鬱效果；佛氏完全佐劑經由皮下注射至大白鼠右後腳掌底板來產生發炎性疼痛；腎上腺皮質酮經由皮下注射且持續21天來產生長期性壓力；西方墨點法用來檢驗在發炎性疼痛或長期壓力下，類鴉片delta受體蛋白質在大白鼠海馬迴的細胞膜上的改變。另外，拮抗劑實驗則用來確認類鴉片delta受體所產生的抗憂鬱效果。實驗結果顯示，大白鼠在正常情境下，SNC80及amitriptyline皆能產生抗憂鬱效果；然而在發炎性疼痛下，SNC80所產生的抗憂鬱效果有提高的表現，並且類鴉片delta受體蛋白質的數量在海馬迴的細胞膜上也隨著疼痛的時間增長而增加，amitriptyline則跟正常情境下的效果相似。另外，大白鼠在長期性壓力下，SNC80的抗憂鬱效果則沒有提高的表現，並且類鴉片delta受體蛋白質的數量在海馬迴的細胞膜上也未受到改變。本研究透過行為實驗提出類鴉片delta受體制效劑的藥理特性，並用分子生物學的方法來對應行為實驗的結果。本研究可做為未來類鴉片delta受體制效劑在治療慢性疼痛的憂鬱症患者上，可能發展為抗憂鬱藥的一個證據。 / Depression is one of the most prevalent mental illnesses all over the world. Patients with chronic pain or stress often have depression. Previous studies have shown that delta opioid receptor (DOR) agonists produced antidepressant-like effects in animal models and that antihyperalgesic effects of DOR agonists can be enhanced in rats under inflammatory pain. The aim of the study was to investigate and compare the antidepressant-like effects of a DOR agonist, SNC80, and a tricyclic antidepressant, amitriptyline, following intracerebroventricular (i.c.v.) administration in rats under different states. The forced swim test was used to determine the antidepressant-like effects of test compounds. Complete Freund’s adjuvant was injected subcutaneously into the right hind paw of rats to elicit inflammatory pain. Corticosterone was injected subcutaneously once per day for 21 days to induce chronic stress. The western blot was used to quantify the levels of DOR protein on plasma membrane in the hippocampus of rats under inflammatory pain or chronic stress. In addition, antagonist experiment was conducted to verify the receptor mechanism underlying the antidepressant-like effects of DOR agonist. Results indicated that i.c.v. SNC80 and amitriptyline dose-dependently produced antidepressant-like effects in rats under normal state. More importantly, the potency of SNC80-induced antidepressant-like effects, but not amitriptyline, was enhanced in rats under inflammatory pain. In addition, up-regulation of supraspinal DORs was time-dependently associated with enhanced antidepressant-like effects of SNC80 in rats under inflammatory pain. On the other hand, SNC80 did not produce enhanced antidepressant-like effects, and DOR density was not changed in rats under chronic stress. This study provides evidence of the DOR agonist’s state-dependent effects and suggests that DOR agonists may be more effective as potential antidepressants for patients with depression comorbid with chronic pain.