The Role of Amygdala in the Acid Induced Chronic Muscle Pain

慢性肌肉疼痛和其引起之痛覺過敏是難以治療的。利用酸性的生食鹽水(ph=4)重複注射於Sprague-Dawley(SD) 大鼠和許多品系的鼠的腓腸肌會產生持續的機械性痛覺過敏和慢性肌肉疼痛。此實驗研究杏仁核的活化與杏仁核T 型態鈣離子通道對於這種長期痛覺敏之發展的必要性。我們利用ERK 免疫化學組織染色和正子斷層描 (PET) 來證實在酸誘導肌肉疼痛的動物中杏仁核受到活化。並經預埋大鼠雙側杏仁核的鋼管，注射兩種T型態鈣離子通道的阻斷mibefradil和ethosuximide，可以防止SD大鼠在重複的注射酸性生食鹽水之後，對機械性刺激反應閾值下降的情形。綜合以上結果顯，杏仁核對於長期肌肉疼痛的產生上扮演重要角色。Chronic muscle pain and hyperalgesia induced are disabling and difficult to treat.cidic Saline (pH=4.0) injected repeatedly into the gastrocnemius muscle produceersistent mechanical hyperalgesia and muscle pain in Sprague-Dawley (SD) rats andany mice strains. The objective of the present project was to test the hypothesis thatctivation of amygdala and amygdala T-type calcium channel is necessary in theevelopment of this chronic hyperalgesia. We used the ERK immunochemistry stainnd positron emission tomography (PET) scanner to demonstrate that activation of themygdale in acid induced pain animals. Cannula was implanted bilaterally in bothide of the amygdala of SD rats and two kinds of T-type calcium channel blockers, namely, mibefradil and ethosuximide, were injected. SD rats showed decrease ofhreshold to mechanical stimulation after repeated injection of acidic saline, and this sensitization phenomenon was prevented by pre-treatment of T-type calcium channel blockers in amygdale. The preliminary results suggest that amygdala play an important role in the expression of chronic muscle pain.中文摘要................................................. 1文摘要................................................. 2一章 前言.............................................. 3.痛覺的傳遞路徑......................................... 3.酸誘導痛覺過敏現像..................................... 4.杏仁核與其傳輸路徑在痛覺傳遞上所扮演的角色............. 5.1.Spino-parabrachio-amygdaloid pain pathway............ 6.2.杏仁核中央區與痛覺之相關性........................... 7.T型鈣離子通道在疼痛中所扮演的角色...................... 8.研究目的............................................... 9二章 材料與方法....................................... 11.受試者................................................ 11.腦部手術.............................................. 11.藥品與藥物顱內注射.................................... 12.肌肉疼痛動物模式之誘導................................ 12.行為測試.............................................. 13.免疫組織化學染色...................................... 14.正子斷層造影.......................................... 15.統計分析.............................................. 16三章 實驗結果......................................... 17.重複注射酸性生理食鹽水於腓腸肌中導致雙側長期疼痛敏感化之現象.....................................................17.重複注射酸性生理食鹽水誘導杏仁核中ERK的活化........... 18. PET掃描影像顯示重複注射酸後杏仁核不對稱活化.......... 19.杏仁核內注射T型態鈣離子通道阻斷劑對於機械性痛覺敏感化之影響...................................................... 20.組織切片.............................................. 21四章 討論............................................. 22.酸誘導慢性肌肉疼痛大鼠動物模式之重建.................. 22.杏仁核中ERK活化與酸誘導之慢性肌肉疼痛之關係........... 23. PET 掃描影像重複證實杏仁核與酸誘導慢性肌肉疼痛之關係. 25.杏仁核T 型態鈣離子通道與酸誘導慢性肌肉疼痛之關係...... 27考文獻................................................ 29錄.................................................... 3