神經星狀膠細胞對急慢性疼痛敏感化和鴉片類耐受性之影響及可能之治療策略

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Title:	神經星狀膠細胞對急慢性疼痛敏感化和鴉片類耐受性之影響及可能之治療策略
Authors:	溫永銳(Yeong-Ray Wen);孫維仁;王嘉銓
Contributors:	醫學院醫學系學士班麻醉學科;中國附醫麻醉部
Date:	2009-07-31
Issue Date:	2012-06-15 11:39:20 (UTC+8)
Abstract:	背景：電針可以廣泛治療各式不同的慢性疼痛，但是許多研究對術後止痛的效果並不一致。本研究將應用我們之前提出的電針止痛模型，在大鼠的手術疼痛模型(Brennan model)上檢驗電針的效果。方法：在氣體麻醉下，SD大鼠接受電針刺激(4Hz, 30分鐘)右腳的足三里穴。大鼠分為數組，包括：1. 控制組：只有針刺無電流，左足底進行蹠部切開手術；2. 單次電針組：在切開手術前接受單次的電針治療；3. 反覆電針組：在切開手術前及手術後兩天，多次接受電針治療；5. Naloxone組：在每次的電針刺激前，均以腹腔注naloxone。所有組別在手術前及手術後數個時間點，測試手術造成腳底的機械性疼痛閾值的變化。同時，為了解電針止痛機制，以免疫組織染色分析脊髓內的神經標記物的改變。結果：電針可以明顯的減輕手術後的觸感痛：單次的電針可以產生一天的止痛效果，而反覆電針可以延長止痛效果，而Naloxone可以完全反轉電針的止痛效果。脊髓染色結果顯示脊髓背角的Fos 蛋白及p-p38活化均被電針刺激所抑制。結論：本研究顯示反覆電針可以加強對大鼠切開手術後的止痛作用，機轉可能是特過興奮內源性嗎啡類物質釋放來減輕疼痛。更重要的是，此治療會抑制中樞神經元活性及神經元與神經膠細胞間的交互作用產生的興奮。 Background: Electroacupuncture (EA) has been accepted to treat muscular pain but its use in post-op-pain is equivocal. In this study, analgesic effect of EA and the possible involvement of p38 activation in spinal glia were investigated in an animal surgical pain model. Methods: Under isoflurane anesthesia, plantar incision (PI) was performed at the left hind paw of adult male SD rats and postoperative tactile allodynia was examined. EA stimulation (4Hz, 0.5 ms, and 10muscle twitch intensity) was delivered at the right ST36 acupoint for 30 min before PI. The control rats received sham needles without electrical current. Two EA protocols were designed: the Pre-EA group had once EA immediately before PI, and the Multi-EA group received EA pretreatment and EA once daily for two postoperative days. Mechanical measurements by von Frey fibers were conducted at several time-points (post-op 1, 3, 5 h, and 1, 2, 3 d, as well as post-EA 1, 3, and 5 h, if applicable). Fos expression and phosphorylated-p38 MAPK activation were analyzed at the postoperative period. Results: PI induced marked mechanical allodynia for 3 days after surgery. Single EA pretreatment produced significant analgesic effect at post-PI 3h, and 1 d, but multiple treatments not only attenuated allodynia but also enhanced analgesia with a prolonging after-effect by the days. Concomitant naloxone completely reversed analgesia. Spinal Fos induction and p-p38 activation was depressed by EA treatment. Conclusions: This study indicates that EA can produced anti-allodynic effect on surgical pain and repeated treatments intensified the analgesia largely through opioid descending system and neuron-glial interactions.
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