Sigma-1R/NOX2调控铁死亡：神经病理性痛的潜在机制

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关键词：神经病理性痛；Sigma-1受体；烟酰胺腺嘌呤二核苷酸磷酸氧化酶2；铁死亡；活性氧中图分类号：R338.2+1文献标志码：A文章编号：2097-7174（2025）11-1093-07DOI：10.3969/j.issn.2097-7174.2025.11.012

Abstract：Neuropathic pain is a pain syndrome caused by damage or disease affecting the somatic sensory nervous system. Dueto its diverse etiologies，protracted course，and complex pathogenesis，it poses significant chalenges for clinical management and has become an urgent public health issue requiring resolution.Sigma-1R（Sigma-1 receptor），as a chaperoneprotein，isactivated under pathologicalstatesand can exertregulatory efects bybinding toreceptors，ion channelsandrelatedkinases.Inaddition，Sigma-1Rmaybeinvolved intheinitiationandmaintenanceof neuropathic pain by activating downstream molecules NOX2（Nicotinamide adenine dinucleotide phosphate （NADPH）oxidase2， NOX2），amemberof the NADPHoxidasefamily that triggers theproductionof ROS，which impacts the progressionof various diseases.Ferroptosis，anovel formof programmedcelldeath，ischaracterizedbyabnormal ironmetabolism， lipid peroxideaccumulation，and glutathione depletion，whichcan beexacerbatedbyNOX2-inducedROS.This review willaddresstherolesand interactions between Sigma-1R/NOX2 signaling pathwayandferoptosis inthedevelopmentof neuropathic pain，and providenovel insights tofurther elucidatethepathogenesisand therapeutic strategiesofneuropathic pain.

Keywords：Neuropathic pain；Sigma-1receptor；Nicotinamideadenine dinucleotidephosphate oxidase2；Ferroptosis; Reactive oxygen species

疼痛是一种早期预警伤害或有害刺激的保护性反应，是机体感受外界伤害性刺激传递的防御信号[1]。（剩余18034字）