Serotonin transporter polymorphism alters citalopram effects on human pain responses to physical pain
Serotonin transporter polymorphism alters citalopram effects on human pain responses to physical pain
复制标题
血清素转运蛋白多态性改变西酞普兰对人体对身体疼痛的疼痛反应的影响
DOI：
10.1016/j.neuroimage.2016.04.064
复制
发表时间：
2016-07-15
期刊：
影响因子：
5.7
通讯作者：
Han, Shihui
中科院分区：
文献类型：
--
作者：
Ma, Yina;Wang, Chenbo;Han, Shihui
人类在疼痛感知方面表现出实质性的个体间差异，这有助于止痛效果的变异性。疼痛敏感性的个体差异与5-羟色胺转运基因（5-HTTLPR）的变异有关，选择性5-羟色胺再摄取抑制剂（SSRIs）如西酞普兰（citalopram）已越来越多地用于治疗多种疼痛状况。我们结合疼痛电刺激时的基因分型、药理学挑战和神经影像学来揭示5 -羟色胺基因和药理学如何相互作用影响疼痛感知及其潜在的神经生物学机制。在一个双盲、安慰剂对照的过程中，我们在功能MRI中对短/短（s/s）和长/长（l/l）健康男性5-HTTLPR纯合子急性给予西酞普兰（30mg / po），同时伴有疼痛和非疼痛电刺激。5-HTTLPR基因型调节西酞普兰对丘脑、小脑、脑岛前部、中扣带皮层和额叶下皮层疼痛相关脑反应的影响。具体来说，西酞普兰显著降低了l/l而非s/s纯合子的疼痛相关脑反应。此外，5-HTTLPR基因型与疼痛相关的大脑活动之间的相互作用是西酞普兰引起的疼痛报告减少的一个很好的预测指标。西酞普兰对全脑疼痛处理的遗传调节与对神经疼痛特征的显著影响是平行的，神经疼痛特征是一种被证实对身体疼痛敏感和特异性的多变量大脑模式。这项工作提供了神经生物学机制，通过遗传变异塑造大脑对疼痛感知和治疗效果的反应。这些发现对于需要5 -羟色胺能治疗有效缓解疼痛的个体类型具有重要意义，这对于推进个性化疼痛治疗至关重要。(C) 2016 Elsevier Inc.版权所有。
Humans exhibit substantial inter-individual differences in pain perception, which contributes to variability in analgesic efficacy. Individual differences in pain sensitivity have been linked with variation in the serotonin transporter gene (5-HTTLPR), and selective serotonin reuptake inhibitors (SSRIs) such as citalopram have been increasingly used as treatments for multiple pain conditions. We combined genotyping, pharmacological challenge, and neuroimaging during painful electrical stimulation to reveal how serotonin genetics and pharmacology interact to influence pain perception and its underlying neurobiological mechanisms. In a double-blind, placebo-controlled procedure, we acutely administrated citalopram (30 mg po) to short/short (s/s) and long/long (l/l) healthy male 5-HTTLPR homozygotes during functional MRI with painful and non-painful electrical stimulation. 5-HTTLPR genotype modulated citalopram effects on pain-related brain responses in the thalamus, cerebellum, anterior insula, midcingulate cortex and inferior frontal cortex. Specifically, citalopram significantly reduced pain-related brain responses in l/l but not in s/s homozygotes. Moreover, the interaction between 5-HTTLPR genotype and pain-related brain activity was a good predictor of the citalopram-induced reductions in pain reports. The genetic modulations of citalopram effects on brain-wide pain processing were paralleled by significant effects on the Neurological Pain Signature, a multivariate brain pattern validated to be sensitive and specific to physical pain. This work provides neurobiological mechanism by which genetic variation shapes brain responses to pain perception and treatment efficacy. These findings have important implications for the types of individuals for whom serotonergic treatments provide effective pain relief, which is critical for advancing personalized pain treatment. (C) 2016 Elsevier Inc. All rights reserved.