| Title | Serotonin transporter polymorphism alters citalopram effects on human pain responses to physical pain |
| Authors | Ma, Yina Wang, Chenbo Luo, Siyang Li, Bingfeng Wager, Tor D. Zhang, Wenxia Rao, Yi Han, Shihui |
| Affiliation | Peking Univ, Dept Psychol, Beijing 100080, Peoples R China. Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing 100080, Peoples R China. Peking Univ, Beijing Key Lab Behav & Mental Hlth, Beijing 100080, Peoples R China. Peking Univ, Sch Life Sci, Peking Tsinghua Ctr Life Sci, Beijing 100080, Peoples R China. Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China. Univ Colorado, Dept Psychol, Campus Box 345, Boulder, CO 80309 USA. Peking Univ, Dept Psychol, Beijing 100080, Peoples R China. Ma, YN (reprint author), Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. |
| Keywords | SSRI 5-HTTLPR fMRI Pain perception Personalized medicine HUMAN BRAIN 5-HTTLPR POLYMORPHISM SUBJECTIVE EXPERIENCE GENE POLYMORPHISM INDIVIDUAL-DIFFERENCES PROMOTER POLYMORPHISM SOMATOSENSORY CORTEX THERMAL HYPERALGESIA NEURAL MECHANISMS HEALTHY-SUBJECTS |
| Issue Date | 2016 |
| Publisher | NEUROIMAGE |
| Citation | NEUROIMAGE.2016,135,186-196. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/433892 |
| ISSN | 1053-8119 |
| DOI | 10.1016/j.neuroimage.2016.04.064 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 心理与认知科学学院 生命科学学院 行为与心理健康北京市重点实验室 |
