2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38539Many chronic pain conditions are an expression of neuronal plasticity. Strong input from the pheriphery to the spinal cord leads to central sensitization, which is associated with hyperexcitability of dorsal horn neurons that likely contributes to increased pain sensitivity. A-type potassium currents are critical determinants of neuronal excitability in the central nervous system. Noradrenergic neurons in the A7 play an important role on the modulation of pain in the descending inhibitory pathway. We have recently provided electrophysiological evidences, which show that A-type potassium currents can be recorded in the noradrenergic neurons of A7. However, little is known about which subunits of voltage-dependent potassium channels will arise to A-type potassium currents, and whether changes in the excitability of A7 noradrenergic neurons can be modulated by any internal protein kinases or external pain modulators through signaling pathway or neuronal circuits. To gain an understanding of the above questions, the present study will investigate: 1) which subunits of voltage-dependent potassium channel will arise to A-type potassium currents, 2) whether internal modulators, such as protein kinase C (PKC), protein kinase A (PKA) and extracellular signal-regulated kinases (ERKs), will modulate A-type potassium currents, 3) whether external pain modulator, such as enkephalin or substance P, will regulate A-type potassium currents, 4) whether non-noradrenergic neurons in the A7 will control A-type potassium currents by synaptic transmission? We believe the results of these experiments will immediately give us a better knowledge of the characteristics of neurons in the A7. Furthermore, this information may shed some light on the understanding how the A7 noradrenergic neurons through widespread neuronal projections to control the transmission of nociception.許多慢性疼痛是一種神經可塑性(neuronal plasticity)的表現。強烈的訊息從週邊傳至中樞 所引起的中樞敏感化(central sensitivity)，往往伴隨著脊髓背角之神經元過度的興奮，最後造 成痛覺敏感性(pain sensitivity)的增加。在中樞神經系統中，A 型鉀離子電流(A-type potassium currents)則被認為是控制神經細胞興奮性的指標代表。在下行痛覺修飾路徑中，A7 區域的正 腎上腺素神經元扮演一重要的角色。我們最近的電生理證據顯示，這些A7 區域的正腎上腺 素神經細胞含有A 型鉀離子電流。然而我們對於A7 區域的正腎上腺素神經細胞，構成其A 型鉀離子電流的voltage-dependent potassium channel 次單元的組成則尚未明瞭。另外，對於細 胞內的蛋白分子、細胞外之痛覺調節因子，是否會透過訊息傳導路徑與複雜的神經網路，控 制A7 區域的正腎上腺素神經細胞的興奮性，而達到抗疼痛的反應也不明瞭。?釐清以上疑 問，本計劃將探討：（1）A7 區域之正腎上腺素神經元其A 型鉀離子電流是由哪些種類voltagedependent potassium channel 的次單元所組成？（2）A7 區域之正腎上腺素神經細胞其A 型鉀 離子電流是否也受到細胞內之蛋白訊息分子，如protein kinase C (PKC)、protein kinase A (PKA) 與extracellular signal-regulated kinases (ERKs)的調控？（3）內生性之痛覺調節因子，如 enkephalin、substance P…等，是否能經由調節A 型鉀離子電流之離子通道功能，進而調節 A7 的正腎上腺素神經細胞的興奮性？（4）A7 區域之非正腎上腺素神經元是否會透過突觸傳 導，進而影響A 型鉀離子電流之離子通道功能？ 我們相信這些實驗的結果將會立即地給予我們對於A7 區域的神經細胞特性有更好的認 識。並且，這些訊息將得以使我們瞭解A7 區域細胞如何透過其複雜的神經網路，來達到抗 疼痛之反應。A7正腎上腺素A 型鉀離子電流突觸抗疼痛A7noradrenalineA-type potassium currentsynapseantinociceptionProject