Wu Fancan, He Wanyou, Song Da, Wu Zhen, Dai Peng, Zheng Xueqin, Wang Hanbing, Xie Chao
Department of Anesthesiology, The First People's Hospital of Foshan, Foshan, Guangdong, PR China.
Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China.
J Control Release. 2025 Mar 10;379:266-284. doi: 10.1016/j.jconrel.2025.01.028. Epub 2025 Jan 13.
Chronic pain is a prevalent condition affecting a significant portion of the global population and is known to be associated with an increased risk of cardiovascular diseases. Despite the clinical relevance, the mechanisms underlying the link between chronic pain and myocardial ischemia-reperfusion (MI/R) injury remain poorly understood. This study aimed to investigate the role of the superior cervical ganglion (SCG) in mediating the effects of chronic pain on MI/R injury and to develop a novel therapeutic strategy. We identified that chronic pain upregulated TNF-α expression and induced hyperactivity in SCG sympathetic neurons, exacerbating MI/R injury. To address this, we engineered an injectable Pluronic/alginate-based composite hydrogel loaded with celecoxib and ropivacaine (celecoxib@Laponite-dopamine-alginate-Pluronic F-127@ropivacaine, CLDAFR). This hydrogel was designed to target the SCG, providing a localized and sustained release of the therapeutic agents, thereby mitigating neuronal inflammation and inhibiting neuronal hyperactivity. The CLDAFR hydrogel demonstrated excellent biocompatibility, heat-sensitive gelation properties, and controlled drug release in vitro. In vivo studies showed that applying CLDAFR effectively reduced MI/R injury in a chronic pain model by suppressing TNF-α expression and SCG neuronal activity. In conclusion, the CLDAFR hydrogel represents a promising therapeutic material for treating chronic pain-exacerbated MI/R injury by precisely targeting the SCG and providing a sustained anti-inflammatory and analgesic effect.
慢性疼痛是一种普遍存在的病症，影响着全球相当一部分人口，并且已知与心血管疾病风险增加有关。尽管具有临床相关性，但慢性疼痛与心肌缺血再灌注（MI/R）损伤之间联系的潜在机制仍知之甚少。本研究旨在探讨颈上神经节（SCG）在介导慢性疼痛对MI/R损伤影响中的作用，并开发一种新的治疗策略。我们发现慢性疼痛上调了TNF-α的表达，并诱导了SCG交感神经元的活动亢进，加剧了MI/R损伤。为了解决这个问题，我们设计了一种负载塞来昔布和罗哌卡因的可注射的基于普朗尼克/藻酸盐的复合水凝胶（塞来昔布@锂皂石-多巴胺-藻酸盐-普朗尼克F-127@罗哌卡因，CLDAFR）。这种水凝胶旨在靶向SCG，实现治疗药物的局部和持续释放，从而减轻神经元炎症并抑制神经元活动亢进。CLDAFR水凝胶在体外表现出优异的生物相容性、热敏凝胶化特性和可控的药物释放。体内研究表明，应用CLDAFR可通过抑制TNF-α表达和SCG神经元活动，有效减轻慢性疼痛模型中的MI/R损伤。总之，CLDAFR水凝胶通过精确靶向SCG并提供持续的抗炎和镇痛作用，代表了一种治疗慢性疼痛加剧的MI/R损伤的有前景的治疗材料。
