目的:观察倍他米松二丙酸酯-聚乙二醇-聚乳酸(B DP-PEG-PLA)微球对大鼠坐骨神经慢性缩窄性损伤(CCI)所致神经病理性疼痛的镇痛作用,及对脊髓细胞外信号调节激酶(ERK)的影响。方法制备3种B DP-PEG-PLA微球,分别以PLA的数均分子量20、30和70 k D表示。96只雄性Wistar大鼠随机分6组(n=16):假手术组(SH组)、模型组(CCI组)、倍他米松二丙酸酯组(BDP组)、20kD组、30kD组和70kD组。观察术前1d,术后3、5、7、10、13及15 d的机械缩足反射阈值(MWT)、热缩足反射潜伏期(TWL)。免疫组化方法检测术后3 d和10 d脊髓磷酸化ERK表达。结果与CCI组相比,B DP组抑制痛觉过敏(MWT下降和TWL缩短)持续至5 d (P<0.05);20 k D组、30 k D组和70 k D组抑制痛觉过敏分别持续至7、10和13 d(P均<0.05)。与CCI组相比, B DP组、20 k D组、30 k D组和70 k D组术后3 d时脊髓Ⅰ~Ⅱ板层磷酸化ERK表达均减少(P均<0.05),70 k D组术后10 d较CCI组和B DP组磷酸化ERK表达减少(P<0.05)。结论坐骨神经单次注射B DP-PEG-PLA微球能通过抑制大鼠脊髓ERK的活性达到长效镇痛作用,且与微球数均分子量有关。
严重的术后疼痛会使患者感到焦虑紧张、睡眠不足甚至影响术后恢复。全身应用阿片类药物是当前的主要镇痛手段,但其副作用(如恶心、呕吐、便秘和呼吸抑制等)会增加患者的不适,延缓患者的恢复时间。相比之下,区域阻滞技术因其副作用少,镇痛效果显著,逐渐成为围术期疼痛管理的重要方法。然而,目前常用的长效局麻药物如罗哌卡因和布比卡因,单次注射的镇痛时间有限,难以满足术后镇痛的需求。为延长区域阻滞的作用时间,研究者提出了多种策略,包括使用连续外周神经阻滞;添加右美托咪定、地塞米松等佐剂;创新药物输送系统和应用纳米技术等为延长局麻药的镇痛时间提供了新方向。本文综述了这些前沿技术的最新研究进展,以期为临床应用提供参考。Severe postoperative pain can cause anxiety, sleep disturbances, and even affect postoperative recovery. Systemic opioid administration is the primary method for pain relief, but its side effects, such as nausea, vomiting, constipation, and respiratory depression, can increase patient discomfort and delay recovery. In contrast, regional block techniques, due to their fewer side effects and significant analgesic effects, have gradually become an important method for perioperative pain management. However, commonly used long-acting local anesthetics, such as ropivacaine and bupivacaine, have limited analgesic duration with a single injection, making them insufficient to meet the needs for postoperative pain control. To extend the duration of regional block, various strategies have been proposed, including the use of continuous peripheral nerve blocks, the addition of adjuvants such as dexmedetomidine and dexamethasone, innovative drug delivery systems, and the application of nanotechnology. These approaches provide new directions for prolonging the analgesic effects of local anesthetics. This review summarizes the latest research advancements in these cutting