Neurological Institute of Jiangxi Province and Department of Neurology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, and Xiangya Hospital of Central South University at Jiangxi, Nanchang, Jiangxi, China.
Jiangxi Mental Hospital, Nanchang University, Nanchang, Jiangxi, China.
J Oral Rehabil. 2024 Dec;51(12):2513-2528. doi: 10.1111/joor.13847. Epub 2024 Aug 29.
Inhibition of astrocytic energy metabolism alleviates neuropathic pain.
To explore whether astrocyte-neuron lactate shuttle (ANLS) played any role in neuropathic orofacial pain.
Rats with partial transection of the right infraorbital nerve (p-IONX) or sham operation were intrathecally injected with acetazolamide (a carbonic anhydrase inhibitor), bithionol (a soluble adenylyl cyclase inhibitor), α-cyano-4-hydroxycinnamic acid [α-CHCA, a monocarboxylate transporter (MCT) inhibitor] or vehicle once a day from postoperative day 1-14. The facial mechanical thresholds were tested on preoperative day 1 and 2 and postoperative days 1, 3, 5, 7, 10 and 14, expression of glucose transporters (GLUTs) and MCTs in the trigeminal subnucleus caudalis (Vc) were examined on the postoperative day 3 and neuronal activities in the Vc were examined in the p-IONX rats on postoperative days 3-5.
Compared with the sham group, the mechanical thresholds in the p-IONX group were significantly reduced at postoperative days 1-7, and the number of astrocytes expressing GLUT1 and MCT1/4, and neurons expressing MCT2 was significantly increased on postoperative day 3. In the p-IONX groups, neurons in the Vc were sensitised, and acetazolamide, bithionol and α-CHCA reversed the central sensitisation, significantly increased the mechanical thresholds at postoperative days 1-7 and decreased the number of astrocytes expressing GLUT1 and MCT1/4, and neurons expressing MCT2 at postoperative day 3 compared with those in the vehicle-treated rats.
Inhibition of ANLS alleviates p-IONX-related neuronal, behavioural and immunohistochemical changes, which suggests that ANLS plays an important role in trigeminal neuropathic pain.
抑制星形胶质细胞能量代谢可减轻神经性疼痛。
探讨星形胶质细胞-神经元乳酸穿梭（ANLS）是否在神经性口面部疼痛中发挥作用。
眶下神经部分横断（p-IONX）或假手术大鼠术后第 1 天至第 14 天每天鞘内注射乙酰唑胺（碳酸酐酶抑制剂）、双羟萘酸噻吩（可溶性腺苷酸环化酶抑制剂）、α-氰基-4-羟基肉桂酸[α-CHCA，单羧酸转运体（MCT）抑制剂]或载体。术前第 1 天和第 2 天以及术后第 1、3、5、7、10 和 14 天测试面部机械阈值，术后第 3 天检测三叉神经尾核（Vc）中葡萄糖转运体（GLUTs）和 MCTs 的表达，术后第 3-5 天检测 p-IONX 大鼠 Vc 中的神经元活动。
与假手术组相比，p-IONX 组在术后第 1-7 天机械阈值显著降低，术后第 3 天 GLUT1 和 MCT1/4 表达的星形胶质细胞和 MCT2 表达的神经元数量显著增加。p-IONX 组 Vc 中的神经元致敏，乙酰唑胺、双羟萘酸噻吩和 α-CHCA 逆转了中枢致敏，显著增加了术后第 1-7 天的机械阈值，降低了术后第 3 天 GLUT1 和 MCT1/4 表达的星形胶质细胞和 MCT2 表达的神经元数量。
抑制 ANLS 可减轻 p-IONX 相关的神经元、行为和免疫组织化学变化，提示 ANLS 在三叉神经病理性疼痛中起重要作用。
