Roy Tapas Kumar, Uniyal Ankit, Tiwari Vinod
Neuroscience & Pain Research Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, 221005, Varanasi, U.P, India.
Mol Biol Rep. 2022 Dec;49(12):12121-12132. doi: 10.1007/s11033-022-07748-9. Epub 2022 Jul 17.
Burn injuries are among the highly prevalent medical conditions worldwide that occur mainly in children, military veterans and victims of fire accidents. It is one of the leading causes of temporary as well as permanent disabilities in patients. Burn injuries are accompanied by pain that persists even after recovery from tissue damage which puts immense pressure on the healthcare system. The pathophysiology of burn pain is poorly understood due to its complex nature and lack of considerable preclinical and clinical shreds of evidence, that creates a substantial barrier to the development of new analgesics. Burns damage the skin layers supplied with nociceptors such as NAV1.7, TRPV1, and TRPA1. Burn injury-mediated co-localization and simultaneous activation of TRPA1 and TRPV1 in nociceptive primary afferent C-fibers which contributes to the development and maintenance of chronic pain. Burn injuries are accompanied by central sensitization, a key feature of pain pathophysiology mainly driven by a series of cascades involving aberrations in the glutamatergic system, microglial activation, release of neuropeptides, cytokines, and chemokines. Activation of p38 mitogen-activated protein kinase, altered endogenous opioid signaling, and distorted genomic expression are other pathophysiological factors responsible for the development and maintenance of burn pain. Here we discuss comprehensive literature on molecular mechanisms of burn pain and potential targets that could be translated into near future therapeutics.
烧伤是全球范围内高度普遍的医学病症之一，主要发生在儿童、退伍军人和火灾事故受害者身上。它是导致患者暂时和永久性残疾的主要原因之一。烧伤会伴随疼痛，即使在组织损伤恢复后疼痛仍会持续，这给医疗系统带来了巨大压力。由于烧伤疼痛的性质复杂且缺乏大量临床前和临床证据，其病理生理学尚未得到充分理解，这为新型镇痛药的开发造成了重大障碍。烧伤会损害由伤害感受器（如NAV1.7、TRPV1和TRPA1）供应的皮肤层。烧伤介导的TRPA1和TRPV1在伤害性初级传入C纤维中的共定位和同时激活，这有助于慢性疼痛的发展和维持。烧伤伴随着中枢敏化，这是疼痛病理生理学的一个关键特征，主要由一系列涉及谷氨酸能系统异常、小胶质细胞激活、神经肽、细胞因子和趋化因子释放的级联反应驱动。p38丝裂原活化蛋白激酶的激活、内源性阿片类信号的改变以及基因组表达的扭曲是导致烧伤疼痛发展和维持的其他病理生理因素。在这里，我们讨论了关于烧伤疼痛分子机制和潜在靶点的综合文献，这些靶点有望在不久的将来转化为治疗方法。
