癌痛是一个全球性的健康问题,随着对癌痛分子机制的深入了解,研究者发现癌痛不仅是肿瘤的结果,同时还对肿瘤的发展具有促进作用.癌痛伴随降钙素基因相关肽(calcitonin gene related peptide,CGRP)、内皮素B受体(endothelin B receptor,ETBR)、原肌球蛋白受体激酶A(tropomyosin-receptor kinase A,TrkA)、电压门控钠离子通道1.3(voltage-gated sodium channel 1.3,Nav1.3)、Nav1.7、Nav1.9、P物质(substance P,SP)、神经激肽-1受体(neurokinin-1 receptor,NK-1R)、瞬时受体电位通道蛋白A1(transient receptor potential A1,TRPA1)和瞬时受体电位香草酸亚型1(transient receptor potential vanilloid 1,TRPV1)等多种"癌痛信号分子"的激活,可通过影响肿瘤微环境中细胞外基质机械强度、酸碱度、钙离子浓度以及活性氧含量等,为肿瘤的增殖、侵袭和转移提供有利条件;同时,肿瘤微环境中的多种细胞也会通过释放化学信号、产生机械刺激增强癌痛信号分子的作用.本文总结了癌痛信号分子在重塑肿瘤微环境中的关键作用以及促进肿瘤恶性进展的过程,揭示"肿瘤-癌痛-肿瘤微环境-肿瘤进展"的交互机制,为癌痛的有效管理和肿瘤治疗策略的创新提供重要的理论支撑和研究方向.
The remodeling effect of cancer pain signaling molecules on the tumor microenvironment
Cancer pain is a global health issue.With a deeper understanding of the molecular mechanisms underlying cancer pain,researchers have found that cancer pain is not only a consequence of tumor development but also plays a role in promoting tumor growth.Cancer pain is accompanied by the activation of various"cancer pain signaling molecules"such as calcitonin gene related peptide(CGRP),endothelin B receptor,(ETBR),tropomyosin-receptor kinase A(TrkA),voltage-gated sodium channel 1.3(Nav1.3),Nav1.7,Nav1.9,substance P(SP),neurokinin-1 receptor(NK-1R),transient receptor potential A1(TRPA1)and transient receptor potential vanilloid 1(TRPV1).These molecules can influence the mechanical strength of the extracellular matrix,pH,Ca2+concentration,and reactive oxygen species content in the tumor microenvironment,providing favorable conditions for tumor proliferation,migration,and invasion.Simultaneously,various cells in the tumor microenvi-ronment can enhance the effects of cancer pain signaling molecules by releasing chemical signals and generating mechanical stimulation.This review summarizes the crucial role of cancer pain signaling molecules in remodeling the tumor microenvironment and promoting the malignant progression of tumors.It reveals the interactive mech-anism of tumor-cancer pain-tumor microenvironment-tumor progression,providing important theoretical support and research directions for the effective management of cancer pain and the innovation of tumor treat-ment strategies.
cancer paintumortumor microenvironmentresponse to painsensory perception of pain
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