電刺激周邊及視丘來探討大鼠傷害覺從視丘至皮質的連結

Abstract

大鼠的傷害覺會從周邊傳導至視丘，再繼續向上至大腦皮質。其中後腳掌在視丘的傷害覺體表映射，主要位於後核（posterior nucleus, Po）與腹後外側核（ventral posterolateral nucleus, VPL），本研究聚焦在VPL至大腦初級體感覺皮質區（Primary somatosensory cortex, SI）的路徑。由於傷害覺反應訊號的信雜比相當低，加上傷害性刺激會使周邊組織損傷，難以利用重複性刺激來做訊號平均以提高信雜比。因此本研究希望能跳過周邊，在傳導中繼站視丘施加深腦電刺激（deep brain stimulation, DBS），施以重複性刺激，在皮質得到良好的反應訊號。 本研究第一階段，先對大鼠左後腳掌施加傷害性周邊電刺激（peripheral electrical stimulation, pES），並在VPL與SI記錄誘發電位，並同時在VPL尾部（caudal VPL, cVPL）搜尋並記錄映射位置。第二階段，對於確定的VPL映射位置施加DBS，並在SI記錄誘發電位。使用相關係數分析pES在SI引發的誘發電位（pES-SI）和DBS視丘在SI引發的誘發電位（DBS-SI），兩者之間的相關性。 研究結果顯示，周邊電刺激在SI的誘發電位，與自然形式刺激的反應可相對應，因此電刺激可用來引發觸覺與傷害覺反應。第二部分，後肢傷害覺在cVPL的體表映射可以分為內側與外側兩個區塊。經由cVPL DBS實驗可以發現，DBS cVPL外側區得到之DBS-SI與pES-SI，兩者之相關性相當高，因此可以推論出cVPL外側區應是會直接投射至SI。而DBS cVPL內側區得到之DBS-SI與pES-SI，兩者之的相關程度並不高，因此cVPL內側區應會投射至SI以外的腦區。加上觸覺與傷害覺在cVPL內、外區塊的映射差異，可以推測cVPL外側區應是作為定位功能，而cVPL內側區可能傳導的是刺激強度的資訊。研究中也證明DBS用作表淺傷害覺快的反應研究工具的可行性。

Nociception in rats conducts from the periphery to the thalamus, and then to the cerebral cortex. The nociceptive somatotopic map of the hind paw in the thalamus mainly locates in the posterior nucleus (Po) and the ventral posterolateral nucleus (VPL), and we focused on the connection from VPL to SI in this study. The signal-to-noise (S/N) ratio of the nociceptive response is usually quite low. Additionally, noxious stimuli would damage the peripheral tissues. It is difficult to apply repetitive stimuli for signal averaging to improve the S/N ratio. Therefore, we applied deep-brain stimulation (DBS) to the thalamus, the relay of sensory conduction, to bypass the peripheral stimulation in this study. We averaged the responses in SI evoked by repetitive DBS performed on thalamus, and the S/N ratio of the response could be improved. In the first stage of this study, the rat’s left hind paw was applied with noxious peripheral electrical stimulation (pES), and the evoked potentials in SI and VPL and the somatotopic map in caudal VPL were recorded. In the second stage of this study, DBS was applied to the site within the hind paw map of VPL, and the evoked potentials in SI were recorded. And then, we analyzed the correlation coefficient between the evoked potentials in SI evoked by pES (pES-SI) with by DBS (DBS-SI). First, the result shows that the evoked potentials in SI evoked by pES could be compared with the responses evoked by natural stimulation. Therefore, pES could be used to evoke tactile and nociceptive responses. Second, it is found that there are medial and lateral parts in the somatotopic map of nociception in the cVPL. When DBS was applied to the lateral part of cVPL, the correlation between DBS-SI and pES-SI is quite high. It can be inferred that the lateral part of cVPL would project to SI directly. When DBS-SI was obtained by DBS on the medial part of cVPL, the correlation between DBS-SI and pES-SI was quite low. It can be inferred that the medial part of cVPL is unlikely to project to SI. With the difference between tactile and nociceptive projection in medial and lateral part of cVPL, it can be inferred that the lateral part of cVPL would conduct information of localization, while the medial part of cVPL may conduct information about the intensity of stimulation. This study also proved the feasibility of DBS as a tool for nociception studies.