Galanin在正中神經病變疼痛中所扮演的角色

Abstract

雖然許多研究顯示神經傳導物質Galanin與神經病變疼痛有所關聯，但是欠缺有關正中神經傷害後Galanin及其受體數量的變化，更遑論它對正中神經病變疼痛的影響為何，所以本實驗利用正中神經慢性纏繞傷害的動物模式模擬腕隧道症候群，探討Galanin及其受體在上肢神經變病疼痛中的影響。 首先發現在正常大白鼠的背根神經節中，Galanin免疫反應神經元的數量相當地少且都為小型的神經元；但在正中神經慢性纏繞傷害後一週，背根神經節中Galanin免疫反應神經元的百分比會顯著地上升，而其中為中大型神經元的比例有明顯地增多。另外配合雙重免疫標誌發現神經損傷後一週Galanin與TRPV1、P2X3、GAP-43雙重標誌神經元的數量及其佔背根神經節的百分比都有顯著增加。而值得注意的是正中神經慢性纏繞傷害前使用局部麻醉劑 (lidocaine)處理，會使得背根神經節中Galanin免疫反應神經元的數量上升的幅度顯著地減緩。除此之外也發現正中神經慢性纏繞傷害後一週，背根神經節及楔狀神經核內GalR2免疫反應神經元的數量會顯著地高於正常組別。配合螢光金逆向標誌，結果發現神經損傷後楔狀神經核內的GalR2免疫反應神經元大多是投射至丘腦的楔狀丘腦接轉神經元。最後我們研究發現給予GalR2拮抗劑處理，可以改善正中神經病變疼痛行為，也會顯著降低電刺激所引發楔狀神經核內c-Fos神經元的數量。由我們的結果顯示阻斷GalR2訊息的傳遞可能成為減緩神經病變疼痛減緩的重要標的。

Many studies have shown that galanin and neuropathic pain has been associated, but lack of galanin and its receptor changes after the median nerve injury and on the median neuropathic pain. In this study, we used the median nerve chronic constriction injury model to serve as the carpal tunnel syndrome, and to investigate the role of galanin and its receptor in the upper limb neuropathic pain. Present results showed that the galanin-immunoreatice like (-IL) neurons were exclusively small-size DRG neurons in the naïve rats. After a week of the median nerve chronic constriction injury, the percentage of galanin-IL neurons and the proportion of them with medium- and large-size both significantly increase. We also used immunofluorescence (IF) double labeling to investigate the relationship between galanin and pain-related factors: vanilloid receptor subtype 1 (TRPV1), P2X3 and growth-associated protein-43 (GAP-43) in the C6 DRG after a week of the median nerve chronic constriction injury. We found that the number and percentage of the above-mentioned double labeling neurons in the injured DRG all have markedly increased. Futhermore, lidocaine treatment prior to median nerve chronic constriction injury, increase in the number of galanin–IL neurons in the DRG was dramatically slow down. This study also showed that one week after injury the number of galanin receptor 2 (GalR2)-IL neurons in the injured side DRG and cuneate nucleus was significantly higher than those in the normal group. Futhermore, combining fluorogold labeling illustrated that in the cuneate nucleus GalR2-IL neurons dreived mostly from cuneothalamic projection neurons after injury. Finally, our results revealed that the level of allodynia and the number of c-Fos neuron in the cuneate nucleus were both alleviated in the GalR2 antagonist treatment group. The present result suggest that the blocking of galanin receptor 2 may be the target of neuropathic pain relief.