School of Rehabilitation, Kunming Medical University, Kunming, 650500 Yunnan Province, China.
Neural Plast. 2022 Jul 23;2022:6472475. doi: 10.1155/2022/6472475. eCollection 2022.
Low-intensity focused ultrasound (LIFU) is a potential noninvasive method to alleviate allodynia by modulating the central nervous system. However, the underlying analgesic mechanisms remain unexplored. Here, we assessed how LIFU at the anterior cingulate cortex (ACC) affects behavior response and central plasticity resulting from chronic constrictive injury (CCI). The safety of LIFU stimulation was assessed by hematoxylin and eosin (H&E) and Fluoro-Jade C (FJC) staining. A 21-day ultrasound exposure therapy was conducted from day 91 after CCI surgery in mice. We assessed the 50% mechanical withdrawal threshold (MWT) using Von Frey filaments (VFFs). The expression levels of microtubule-associated protein 2 (MAP2), growth-associated protein 43 (GAP43), and tau were determined via western blotting (WB) and immunofluorescence (IF) staining to evaluate the central plasticity in ACC. The regions of ACC were activated effectively and safely by LIFU stimulation, which significantly increased the number of c-fos-positive cells ( < 0.05) with no bleeding, coagulative necrosis, and neuronal loss. Under chronic neuropathic pain- (CNP-) induced allodynia, MWT decreased significantly ( < 0.05), and overexpression of MAP2, GAP43, and tau was also observed. After 3 weeks of treatment, significant increases in MWT were found in the CCI+LIFU group compared with the CCI group ( < 0.05). WB and IF staining both demonstrated a significant reduction in the expression levels of MAP2, GAP43, and tau ( < 0.05). LIFU treatment on ACC can effectively attenuate CNP-evoked mechanical sensitivity to pain and reverse aberrant central plasticity.
低强度聚焦超声（LIFU）是一种有潜力的非侵入性方法，可以通过调节中枢神经系统来缓解痛觉过敏。然而，其潜在的镇痛机制仍未被探索。在这里，我们评估了前扣带皮层（ACC）处的 LIFU 如何影响慢性压迫性损伤（CCI）引起的行为反应和中枢可塑性。通过苏木精和伊红（H&E）和氟-Jade C（FJC）染色评估 LIFU 刺激的安全性。在 CCI 手术后的第 91 天开始，对小鼠进行为期 21 天的超声暴露治疗。我们使用 Von Frey 细丝（VFF）评估 50%机械撤回避（MWT）。通过 Western blot（WB）和免疫荧光（IF）染色测定微管相关蛋白 2（MAP2）、生长相关蛋白 43（GAP43）和 tau 的表达水平，以评估 ACC 中的中枢可塑性。LIFU 刺激有效地和安全地激活了 ACC 区域，这显著增加了 c-fos 阳性细胞的数量（<0.05），且没有出血、凝固性坏死和神经元丢失。在慢性神经病理性疼痛（CNP）诱导的痛觉过敏下，MWT 显著降低（<0.05），并且 MAP2、GAP43 和 tau 的过表达也观察到。经过 3 周的治疗，CCI+LIFU 组的 MWT 显著高于 CCI 组（<0.05）。WB 和 IF 染色均显示 MAP2、GAP43 和 tau 的表达水平显著降低（<0.05）。ACC 上的 LIFU 治疗可以有效减轻 CNP 引起的机械性疼痛敏感性，并逆转异常的中枢可塑性。
