Title
Serotonin transporter polymorphism alters citalopram effects on human pain responses to physical pain.
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 (30mgpo) 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.
Year
DOI
Venue
2016
10.1016/j.neuroimage.2016.04.064
NeuroImage
Keywords
Field
DocType
SSRI,5-HTTLPR,fMRI,Pain perception,Personalized medicine
Serotonergic,Neuroscience,Threshold of pain,Analgesic,Psychology,Serotonin transporter,Reuptake inhibitor,Citalopram,Serotonin Uptake Inhibitors,5-HTTLPR
Journal
Volume
ISSN
Citations 
135
1053-8119
1
PageRank 
References 
Authors
0.35
0
8
Name
Order
Citations
PageRank
Yina Ma1133.20
Chenbo Wang240.83
Siyang Luo331.09
Bingfeng Li430.75
Tor D. Wager565044.38
Wenxia Zhang630.75
Yi Rao730.75
Shihui Han813218.96