Data_Sheet_1.DOCX

Abstract

Pain, as the most prevalent neurological complication of herpes zoster (HZ), may occur before or during the rash onset, or even after the rash has recovered. Particularly, postherpetic neuralgia (PHN) is a refractory chronic condition, usually defined as pain persisting for 3 months or longer from HZ onset. Pain evoked by HZ impairs patients' normal physical and emotional functions, severely reducing their quality of life. However, how zoster associated pain occurs and develops into PHN is elusive, making PHN difficult to predict. Uncovering the pathogenesis of zoster associated pain (or herpetic neuralgia, HN) helps us better understand the PHN onset and supports for developing more effective treatments. Here, we successfully constructed a model for zoster associated pain through varicella-zoster virus (VZV) infections of mouse footpads and pain behavior assessments. Next, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) to analyze PHN rodent dorsal root ganglion (DRG) gene microarray data and found that calcium signal disorder might be involved in the PHN onset. Using reverse transcription real-time fluorescent quantitative PCR (qRT-PCR) and western blotting, we confirmed that VZV infection could significantly up-regulate the expression of T-type calcium channel Cav3.2 in DRG and spinal dorsal horn (SDH). Intrathecal administration of Cav3.2 blocker (2R/S)-6-PNG relieved mechanical and thermal hyperalgesia induced by VZV. Taken together, our data indicated that VZV might participate in the occurrence and development of herpetic neuralgia (HN) by up-regulating the expression of Cav3.2 in DRG and SDH. These findings will help reveal the underlying mechanisms on long-lasting pain and PHN formation, providing a new insight that Cav3.2 can be the promising drug target for remitting PHN.