• J Pain · Mar 2024

    Review

    Serotonin transporter (5-HTT, SERT, SLC6A4) and sodium-dependent reuptake inhibitors (SRIs) as modulators of pain behaviors and analgesic responses.

    • Cary Huang, Andre J van Wijnen, and Hee-Jeong Im.
    • Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, Illinois; Department of Anesthesiology, NewYork-Presbyterian/Weill Cornell Medical Center, New York, New York. Electronic address: chuan40@uic.edu.
    • J Pain. 2024 Mar 1; 25 (3): 618631618-631.

    AbstractThe serotonin transporter (5-hydroxytryptamine transporter [5-HTT], Serotonin Transporter (SERT), SLC6A4) modulates the activity of serotonin via sodium-dependent reuptake. Given the established importance of serotonin in the control of pain, 5-HTT has received much interest in studies of pain states and as a pharmacological target for serotonin reuptake inhibitors (SRIs). Animal models expressing varying levels of 5-HTT activity show marked differences in pain behaviors and analgesic responses, as well as many serotonin-related physiological effects. In humans, functional nucleotide variations in the SLC6A4 gene, which encodes the serotonin transporter 5-HTT, are associated with certain pathologic pain conditions and differences in responses to pharmacological therapy. These findings collectively reflect the importance of 5-HTT in the intricate physiology and management of pain, as well as the scientific and clinical challenges that need to be considered for the optimization of 5-HTT-related analgesic therapies. PERSPECTIVE: The serotonin transporter 5-HTT/SCL6A4 is sensitive to pharmacological SRIs. Experimental studies on the physiological functions of serotonin, as well as genetic mouse models and clinical phenotype/genotype correlations of nucleotide variation in the human 5-HTT/SCL6A4 gene, provide new insights for the use of SRIs in chronic pain management.Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.

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