坐骨神經分支選擇結紮切斷神經性疼痛模式大鼠之腦葡萄糖代謝改變之研究

Abstract

神經性疼痛是體感覺神經系統的損傷所引發的慢性疼痛，自發性疼痛，觸感異常以及痛覺敏感化是神經性疼痛三大徵狀。近期研究指出在神經性疼痛中脊髓以上的中樞神經活性變化對於疼痛的調控扮演很重要的角色。本實驗結合行為測試和搭配氟 18 去氧葡萄糖 (FDG) 為追蹤劑進行正子斷層掃描，探討大鼠在坐骨神經分支選擇結紮切斷 (SNI) 的神經性疼痛痛模型的大鼠腦中葡萄糖代謝活性之變化。SNI 手術後，大鼠表現出自發性疼痛行為，機械性觸感痛覺和熱痛覺敏感至少持續4個禮拜。在 PET 探討自發性疼痛的結果中，大腦葡萄糖代謝活性在 SNI 手術後相比手術前的控制組於對側後島腦區 (posterior insular cortex, PIC) 顯著增加；相比偽手術後控制組於中膈區 (septum) 和 視丘室旁核 (paraventricular thalamic nucleus, PVA) 顯著增加。PIC 之代謝活性與自發性疼痛程度呈顯著相關。在利用 PET 探討機械性觸發異常觸感的結果中，大腦葡萄糖代謝活性在 SNI 手術後相比手術前組的改變於雙側初級體感覺皮層 (primary somatosensory cortex)，對側次級體感覺皮層 (secondary somatosensory cortex)，對側初級運動皮層 (primary motor cortex)， 同側次級運動皮層 (secondary motor cortex) ，下視丘 (hypothalamus) ，前側島腦 (rostral agranular insular cortex, RAIC)，PIC ，小腦 (cerebellum) 顯著增加。實驗結果顯示在大腦的層次，神經性疼痛症狀中的自發性疼痛及觸感痛均有多個腦區參與，其中島腦可能扮演很重要的角色。

Neuropathic pain is triggered by lesions in the somatosensory nervous system. Pain occurs spontaneously and responses to noxious and innocuous stimuli are pathologically amplified. Neural activity in supraspinal centers play an important role in the modulation of pain behavior in neuropathic pain, but the precise mechanism underlying are not fully understood. In this study, we combined behavioural test with positron emission tomography (PET), using 18- fluorode-oxyglucose (18-FDG) as a tracer, to investigate the change of brain glucose metabolic activity in the spared nerve injury (SNI) model of neuropathic pain of the rat. Two major branches of the sciatic nerve were transected under anesthesia condition. After SNI surgery, the rats displayed spontaneous pain behavior, mechanical allodynia and thermal hyperalgesia behavior lasting at least 4 weeks. In PET study of spontaneous paw lifting, glucose metabolic activity in SNI condition was significantly increased in contralateral posterior insular cortex (PIC) compared to pre-surgery control, and significantly increased in septum and paraventricular thalamic nucleus (PVA) compared to sham control. And the glucose metabolic activity of insular cortex correlated linearly with the magnitude of spontaneous paw lifting. In PET study of allodynia, 6 g vonFrey hair was used to stimulus the paw pad of the affected hindlimb. Glucose metabolic activity change in SNI condition was significantly increased in bilateral primary sensory cortex (S1), contralateral secondary sensory cortex (S2), contralateral primary motor cortex (M1), ipsilateral secondary motor cortex (M2), contralateral rostral agranular insular cortex (RAIC)，posterior insular cortex (PIC), hypothalamus, mediodorsal nucleus (MD) of thalamus and cerebellum compared to pre-surgery control. The data suggest that there are many brain areas involved in neuropathic pain, and insular cortex may play an important role in spontaneous pain condition.