中文摘要 痛覺是ㄧ種當身體受到環境中的有害刺激時，所產生的一種不舒服的重要感 覺，也是警告我們身體遭受到傷害，必須規避或治療的一種保護機制。 前人研究發現在海藻醣引發的預發炎模式中，蛋白激?A 與Cε 可能扮演在 急性疼痛轉為慢性疼痛的關鍵角色。此外，組織酸化被認為是造成疼痛的主要原 因之一，但目前還不清楚的是因組織酸化而引起疼痛是透過怎麼樣的下游機制。 此外細胞內的溶血磷脂質是否能引發痛覺，會參與在哪類痛覺的機制中，也仍然 尚未被釐清。 我探究的方式是在小鼠的後肢腳掌皮下注射酸性緩衝溶液與三種溶血磷脂 質，並且分別在各組實驗裡另注射不同訊號傳遞路徑的抑制劑。注射後在不同的 時間點分別用馮法瑞尼龍測量絲以及哈格里夫斯熱感測試儀來做測試，觀察機械 性疼痛和熱感刺激疼痛是否被下游路徑的抑制劑所抑制，以及抑制的程度與時間 區段。實驗發現注射酸以及三類溶血磷脂質都造成機械性與熱感痛覺敏感性增強 的現象並持續超過一天。另外發現蛋白激?A 的抑制劑、AC 之阻斷劑會在疼痛 敏感性上升的初期有抑制作用；蛋白激?Cε 的抑制劑、Gi 之抑制劑、PLC 之阻 斷劑則會在疼痛敏感性上升的中期以後才有抑制作用。有關痛覺的離子通道方面 的ASICs 之阻斷劑、TRP 之阻斷劑，也能抑制機械性和熱感痛覺敏感性升高的 現象。期許在更多的痛覺機制被釐清之後，能被應用在研發緩和痛覺，副作用更 少的藥物上。 Abstract Pain is a complex experience that involves the transduction of noxious environmental stimuli. The ability to detect noxious stimuli is essential to an organism's survival and wellbeing. Some studies have demonstrate that in carrageenan-induced priming state protein kinase A and Cε play critical roles in the transition from acute pain to chronic pain. A decrease in tissue pH has been observed following inflammation, hematomas, and isometric exercise. A positive correlation exists between pain and local acidity. However, the downstream mechanism of proton-induced pain remains unclear. Furthermore, the regulatory pathway between lysophospholipids and pain has not been investigated completely. To answer these questions, I used mechanical and thermal tests in different time period to examine the hyperalgesia induced by acidic solution, psychosine, lysphosphatidylcholine and sphingosylphosphatidylcholine. In addition, protein kinase A inhibitor and adenylyl cyclase blocker inhibit hyperalgesia in the early stage, but protein kinase Cε inhibitor, Gi inhibitor and phospholipase C blocker inhibit hyperalgesia in the middle and late stage. Transient receptor potential family blocker and acid-sensing ion channel blocker also inhibit acid-induced mechanical and thermal hyperalgesia. I wish these studies can be used in pain curation in the future.
