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| Title: | 甜菜鹼對順鉑引發的小鼠神經病理性疼痛之止痛作用及機制探討
Analgesic effects and mechanisms of betaine on cisplatin-induced neuropathic pain in mice |
| Authors: | 羅玉珠
Luo, Yu-Zhu |
| Contributors: | 詹銘煥
陳慧諴
Chan, Ming-Huan
Chen, Hwei-Hsien
羅玉珠
Luo, Yu-Zhu |
| Keywords: | 甜菜鹼
神經病理性疼痛
順鉑
NMDA
Betaine
Neuropathic pain
Cisplatin
NMDA |
| Date: | 2021 |
| Issue Date: | 2021-03-02 14:34:17 (UTC+8) |
| Abstract: | N-methyl-D-aspartate (NMDA)受體調節劑可以緩解神經病理性疼痛。甜菜鹼 亦稱為三甲基甘胺酸 (Trimethylglycine)，具調節 NMDA 受體的作用。本研究採 用順鉑引發神經病理性疼痛的小鼠模型來研究甜菜鹼的鎮痛效果和作用機轉。實 驗採用腹腔注射 (i.p.)、脊髓鞘內注射 (i.t.)、腦室內注射 (i.c.v.) 以及通過於 medial prefrontal cortex 以及通過腦部埋管進行前額葉皮質(mPFC)埋管進行微量 注射藥物後，使用 Von Frey 測試順鉑處理後之小鼠機械性觸覺反應其疼痛程度。 實驗結果顯示，甜菜鹼以腹腔、脊髓鞘內、腦室內注射以及腦內微注射到 mPFC 的方式皆能緩解順鉑引發的小鼠神經病理性疼痛。在其作用機制上，發現以腦室 內注射 NMDA 受體抑制劑 7-chlorokynurenic acid (7-CK)可以抑制甜菜鹼緩解疼 痛的效果，但是以脊髓鞘內注射 7-CK 的方式無法抑制腹腔注射甜菜鹼緩解疼痛 的效果。微注射 7-CK 到 mPFC 可以抑制微注射甜菜鹼到 mPFC 緩解疼痛的效 果，但是無法抑制腹腔注射甜菜鹼緩解疼痛的效果。以腹腔、脊髓鞘內.或腦室內 注射 α2A 腎上腺素受體拮抗劑 yohimbine 的方式能抑制甜菜鹼緩解疼痛的作用。 另外使用管餵 β 受體拮抗劑 propranolol 的方式也能抑制甜菜鹼緩解疼痛的作用。 以腹腔、脊髓鞘內或腦室內注射的方式給予 5-HT1A 受體拮抗劑 WAY100635 能 抑制甜菜鹼緩解疼痛的作用。以脊髓鞘內注射 5-HT7 受體拮抗劑 SB269970 的方 式能抑制甜菜鹼緩解疼痛的作用。但以腦室內注射 SB269970 的方式對甜菜鹼緩 解疼痛的作用沒有影響。以脊髓鞘內或是腦室內注射的方式給予 α7-nAChR 受體 拮抗劑 MLA 能抑制甜菜鹼緩解疼痛的作用。另以脊髓鞘內注射和腦室內注射 α4β2-nAChR 受體拮抗劑 DHβE 能抑制甜菜鹼緩解疼痛的作用。以腹腔、脊髓鞘 內或腦室內注射的方式給予鴉片類受體拮抗劑 naloxone 能抑制甜菜鹼緩解疼痛 的作用。本實驗結果證實甜菜鹼有緩解神經病理性疼痛的作用。其作用位置至少 包含 mPFC 和脊髓，參與甜菜鹼緩解神經病理性疼痛的調控因子包含 NMDA、 正腎上腺素、血清素、乙醯膽鹼以及鴉片類受體。因此，活化下行性疼痛抑制路 徑和脊髓的調節在甜菜鹼緩解順鉑引發的神經病理性疼痛中均扮演重要的角色。
N-methyl-D-aspartate (NMDA) receptor modulators can relieve neuropathic pain. Betaine, also known as trimethylglycine, can regulate NMDA receptor. In this study, a mouse model of cisplatin-induced neuropathic pain was used to study the analgesic effect and mechanism of betaine. After intraperitoneal injection (i.p.), intrathecal injection (i.t.), intraventricular injection (i.c.v.) and micro injection into medial prefrontal cortex (mPFC), von Frey test was used to examine the paw withdrawal threshold (PWT) in the cisplatin-treated mice. The results showed that betaine could alleviate the neuropathic pain induced by cisplatin in mice by i.p., i.t., and i.c.v. injection and microinjection into mPFC. To determine the mechanism of action of betaine, NMDA receptor inhibitor 7-chlorokynurenic acid (7-CK), ) by i.c.v. injection but not by i.t. injection, could inhibit the antiallodynic effect of betaine (i.p.). Microinjection of 7-CK into mPFC could inhibit the pain relief effect of microinjection of betaine into mPFC, but could not inhibit the antiallodynic effect of i.p. injection of betaine. In addition, yohimbine, an α2-adrenoceptor antagonist (i.p., i.t. or i.c.v. injection) could inhibit the analgesic effect of betaine. The antiallodynic effect of betaine was also inhibited by β-adrenoceptor antagonist propranolol. WAY100635, a 5- HT1A receptor antagonist, can inhibit the pain relieving effect of betaine by i.p., i.t. or i.c.v. injection. 5-HT7 receptor antagonist SB269970 inhibited the analgesic effect of betaine by i.t. injection, whereas, i.c.v. injection of SB269970 had no effect. In addition, i.t. injection and i.c.v. injection of the α7-nAChR antagonist MLA and the α4β2-nAChR antagonist DHβE could inhibit the analgesic effect of betaine. Naloxone, an opioid receptor antagonist, could inhibit the antiallodynic effect of betaine by i.p., i.t. or i.c.v. injection. The results showed that betaine could relieve neuropathic pain. The regulatory factors involved in the alleviation of neuropathic pain by betaine include NMDA, adrenergic, serotonergic, cholinergic and opioid receptors. Therefore, activation of descending pain inhibition pathway and regulation of spinal cord play a role in betaine alleviating cisplatin-induced neuropathic pain. |
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| Description: | 碩士
國立政治大學
神經科學研究所
106754002 |
| Source URI: | http://thesis.lib.nccu.edu.tw/record/#G0106754002 |
| Data Type: | thesis |
| DOI: | 10.6814/NCCU202100381 |
| Appears in Collections: | [神經科學研究所 ] 學位論文
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