You Zerong, Jain Shubhika, Shen Shiqian, Mao Jianren, Martyn J A Jeevendra
Department of Anesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, USA.
Shriners Hospital for Children, Boston, MA, USA.
Burns Open. 2025 Apr;10. doi: 10.1016/j.burnso.2025.100396. Epub 2025 Feb 19.
This review examines the pathophysiology and therapeutic management of burn injury-induced pain (BIP). Burn injury, occurring globally in about 11 million people, often induces the most intense pain, but its management remains suboptimal. The pain often persists even after complete wound healing and hospital discharge causing both long-term disability and neurological dysfunction. The fact that BIP persists well beyond the initial hospitalization is not well recognized and should be underscored as the pain involves even non-burned areas. The pathophysiology of the latter problem is poorly understood and needs further study. Opioids, the mainstay for moderate to severe pain relief after major burn injury, with time, have poor analgesic and serious side effects. Accurate assessment pain of BIP and its biology at different stages of treatment helps to provide effective treatments of the different etiological factors that cause BIP and their sequelae. Based on clinical and pre-clinical studies, we discuss the current knowledge on the underlying cellular and molecular mechanisms in the initiation and persistence of BIP during the acute phase and later phases of injury. Opioid receptor-mediated signaling changes and immune microglia responses in concert exaggerate nociceptive behavior. Both burn injury and opioids upregulate spinal NMDA receptor expression and microglia changes, which further exaggerate pain. BIP has inflammatory and neuropathic components. Pharmacological and non-pharmacological approaches currently available for management of BIP is discussed. Areas that need further study include the role of other central and peripheral factors in the exaggeration of pain well beyond wound healing. Novel non-opioid methods to rectify BIP is important to develop in view of the potential for opioid use disorder. The role of microbiome in chronic pain syndromes is an unexplored territory and its relevance to BIP needs further examination. Pruritus or itch, though very common and important in the pharmacotherapy of burns, the discussion of this topic is brief. Extensive review of this topic is beyond the scope of this review in view of the vast body of knowledge and varying and multiple treatment options.
本综述探讨了烧伤性疼痛（BIP）的病理生理学及治疗管理。全球约有1100万人遭受烧伤，烧伤常引发极为剧烈的疼痛，但其治疗效果仍不尽人意。即便伤口完全愈合且患者已出院，疼痛仍常持续存在，导致长期残疾和神经功能障碍。BIP在初次住院后仍长期存在这一事实尚未得到充分认识，鉴于疼痛甚至累及未烧伤区域，应予以强调。后一问题的病理生理学尚不清楚，需要进一步研究。阿片类药物是重度烧伤后缓解中至重度疼痛的主要药物，但随着时间推移，其镇痛效果不佳且副作用严重。准确评估BIP在治疗不同阶段的疼痛及其生物学特性，有助于针对导致BIP及其后遗症的不同病因提供有效的治疗。基于临床和临床前研究，我们讨论了目前关于BIP在损伤急性期及后期起始和持续过程中潜在细胞和分子机制的认识。阿片受体介导的信号变化和免疫小胶质细胞反应共同加剧了伤害感受行为。烧伤和阿片类药物均上调脊髓N - 甲基 - D - 天冬氨酸（NMDA）受体表达及小胶质细胞变化，进而进一步加剧疼痛。BIP具有炎症性和神经性成分。本文讨论了目前可用于管理BIP的药物和非药物方法。需要进一步研究的领域包括其他中枢和外周因素在伤口愈合后疼痛加剧中的作用。鉴于阿片类药物使用障碍的可能性，开发新型非阿片类方法来纠正BIP非常重要。微生物群在慢性疼痛综合征中的作用是一个未被探索的领域，其与BIP的相关性需要进一步研究。瘙痒在烧伤药物治疗中虽然非常常见且重要，但鉴于该主题知识广博且治疗选择多样，本文对此的讨论较为简短。
