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

EAAT-2 下调通过增加带状疱疹感染后的血浆谷氨酸水平来加剧慢性神经性疼痛

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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.

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