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

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 with CNP in HZ patients. This study was conducted with 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, RNA 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. Plasma glutamate levels were significantly elevated in the CNP group. A positive correlation was observed between protein expression and plasma glutamate levels in the CNP group. Decreased EAAT-2 mRNA and protein expression and elevated plasma glutamate levels played a significant role in the development and maintenance of CNP. These findings offer valuable insights into the pathophysiology of CNP after HZ infection and highlight the potential of targeting EAAT-2 for developing novel therapeutic strategies for pain management.