Department of Anesthesiology, Affiliated Hospital and Medical School of Nantong University, No. 20 Xisi Road, Nantong, 226001, Jiangsu, China.
BMC Anesthesiol. 2023 Nov 21;23(1):381. doi: 10.1186/s12871-023-02306-7.
Blood nerve barrier (BNB) participates in the development of neuropathic pain. AQP1 is involved in peripheral pain perception and is negatively correlated with HIF-1α phenotype, which regulates endothelial permeability. However, the role of HIF-1α-AQP1-mediated BNB dysfunction in Chronic Postsurgical Pain (CPSP) has not been reported.
Male Sprague-Dawley rats were randomized into 5 groups: (i) Naive group; (ii) Sham group; (iii) SMIR group: skin/muscle incision and retraction for one hour. Behavioral tests were performed for the three groups, BNB vascular permeability and western blotting were conducted to determine HIF-1α and AQP1 protein expression. (iv) The SMIR + HIF-1α inhibitor group; (v) SMIR + DMSO group. Rats in the two groups were administered with HIF-1α inhibitor (2ME2) or DMSO intraperitoneally on the third day post-SMIR surgery followed by performance of behavioral tests, BNB permeability assessment, and determination of HIF-1α, AQP1 and NF200 protein levels.
The permeability of BNB was significantly increased and the expression of AQP1 was downregulated on the 3rd and 7th days post-operation. AQP1 is mainly located in neurons and NF200, CGRP-positive nerve fibers. HIF-1α was highly expressed on the third day post-operation. HIF-1α inhibitor reversed the decrease in AQP1 expression and increase in NF200 expression, barrier permeability and hyperalgesia induced by SMIR on the 3rd day post-surgery.
Early dysfunction of BNB mediated by HIF-1α/AQP1 activated by SMIR may be an important mechanism to promote acute postoperative painful transformation of CPSP. Preadaptive protection of endothelial cells around nerve substructures may be an important countermeasure to inhibit CPSP transformation. Early impairment of BNB function mediated by HIF-1α/AQP1 activated by SMIR may be an important mechanism for promoting acute postoperative pain transformation of CPSP.
血神经屏障（BNB）参与神经病理性疼痛的发生。水通道蛋白 1（AQP1）参与外周痛觉感知，与负向调节内皮通透性的缺氧诱导因子-1α（HIF-1α）表型呈负相关。然而，SMIR 诱导的 HIF-1α-AQP1 介导的 BNB 功能障碍在慢性术后疼痛（CPSP）中的作用尚未报道。
雄性 Sprague-Dawley 大鼠随机分为 5 组：（i）正常组；（ii）假手术组；（iii）SMIR 组：皮肤/肌肉切开并牵开 1 小时。对三组大鼠进行行为学测试，检测 BNB 血管通透性和 Western blot 以确定 HIF-1α和 AQP1 蛋白表达。（iv）SMIR+HIF-1α 抑制剂组；（v）SMIR+DMSO 组。两组大鼠在 SMIR 手术后第 3 天分别给予 HIF-1α 抑制剂（2ME2）或 DMSO 腹腔注射，然后进行行为学测试、BBB 通透性评估以及 HIF-1α、AQP1 和 NF200 蛋白水平的测定。
术后第 3 天和第 7 天，BBB 通透性显著增加，AQP1 表达下调。AQP1 主要位于神经元和 NF200、CGRP 阳性神经纤维中。术后第 3 天 HIF-1α 高表达。HIF-1α 抑制剂逆转了 SMIR 术后第 3 天引起的 AQP1 表达降低、NF200 表达升高、屏障通透性增加和痛觉过敏。
SMIR 激活的 HIF-1α/AQP1 介导的早期 BNB 功能障碍可能是促进 CPSP 急性术后痛觉转化的重要机制。神经亚结构周围内皮细胞的预适应保护可能是抑制 CPSP 转化的重要对策。SMIR 激活的 HIF-1α/AQP1 介导的早期 BNB 功能障碍可能是促进 CPSP 急性术后痛觉转化的重要机制。
