Downregulation of EAAT-2 impairs chronic neuropathic pain via increasing of plasma glutamate after herpes zoster infection

Abstract Chronic neuropathic pain (CNP) is a debilitating complication of herpes zoster (HZ) with significant impact on quality of life. This study aimed to investigate the association between excitatory amino acid transporter 2 (EAAT-2) expression and plasma glutamate concentrations in HZ patients...

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Bibliographic Details
Main Authors: Li-Na Lu, Li-Hong Mei, Xu-Shuo Li, Ji-Hong Zhang, Gao Yang
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-01501-5
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Summary:Abstract Chronic neuropathic pain (CNP) is a debilitating complication of herpes zoster (HZ) with significant impact on quality of life. This study aimed to investigate the association between excitatory amino acid transporter 2 (EAAT-2) expression and plasma glutamate concentrations in HZ patients with CNP. This study was conducted with 102 consecutive patients diagnosed with HZ. Participants were divided into two groups: CNP (n = 51) and acute pain (ACP, n = 51). Pain severity was assessed using the Numerical Rating Scale. Blood samples were collected for genotype analysis, mRNA and protein extraction, and plasma glutamate measurement. EAAT-2 DNA genotyping was analyzed by polymerase chain reaction (PCR); EAAT-2 mRNA expression was analyzed by quantitative real-time PCR; EAAT-2 protein and glutamate levels were analyzed by enzyme-linked immunosorbent assay. The EAAT-2 DNA showed no significant difference in CNP and ACP patients. CNP patients exhibited lower EAAT-2 mRNA and protein levels compared to ACP patients. However, plasma glutamate levels were significantly elevated in the CNP patients. A correlation was observed between EAAT-2 protein concentration and plasma glutamate levels in the CNP group. This study demonstrates EAAT-2 mRNA downregulation, reduced EAAT-2 protein concentration, and elevated plasma glutamate levels play roles in CNP following HZ infection. These findings suggests that EAAT-2 may be a relevant target for further investigation in therapeutic development.
ISSN:2045-2322