Characterization of plasma metabolites and proteins in patients with herpetic neuralgia and development of machine learning predictive models based on metabolomic profiling

Abstract

Herpes zoster (HZ) is a localized, painful cutaneous eruption that occurs upon reactivation of the herpes virus. Postherpetic neuralgia (PHN) is the most common chronic complication of HZ. In this study, we examined the metabolomic and proteomic signatures of disease progression in patients with HZ and PHN. We identified differentially expressed metabolites (DEMs), differentially expressed proteins (DEPs), and key signaling pathways that transition from healthy volunteers to the acute or/and chronic phases of herpetic neuralgia. Moreover, some specific metabolites correlated with pain scores, disease duration, age, and pain in sex dimorphism. In addition, we developed and validated three optimal predictive models (AUC > 0.9) for classifying HZ and PHN from healthy individuals based on metabolic patterns and machine learning. These findings may reveal the overall metabolomics and proteomics landscapes and proposed the optimal machine learning predictive models, which provide insights into the mechanisms of HZ and PHN.

Cerebrospinal Fluid Proteomic Profiles in Patients with Postherpetic Neuralgia

“…It shall be noteworthy that previous clinical research studies have indicated a correlation between VZV infection and BBB disruption. − In parallel, in the present study, the activated processes and pathways enriched in the PHN-CSF, such as coagulation, complement activation, infection and immune response, phagocytosis, and cholesterol metabolism, were similar to those in previous proteomic research investigating the plasma metabolism of the PHN patients . Besides, PLG and APOA1, the verified hub proteins, are reported to be mainly derived from the bloodstream rather than the CNS.…”

“…PHN is highly characterized by central sensitization, which makes CSF an ideal medium to explore the pathological changes of the disease. Based on our limited knowledge, few proteomic studies have aimed to elucidate the changes during the process of PHN, among which most of these studies were focused on the changes of the blood rather than the CSF. , There was only one proteomic study conducted in 2012 which evaluated the effect of intrathecal steroid administration on protein changes in PHN-CSF. However, the steroid’s action on PHN remains complicated since the steroid treatment has proven to be effective in the short term but not the long term of PHN. − Thus, the steroid-induced protein changes in PHN-CSF might not be the key nodes to elucidate the intrinsic mechanism of PHN.…”

“…Based on our limited knowledge, few proteomic studies have aimed to elucidate the changes during the process of PHN, among which most of these studies were focused on the changes of the blood rather than the CSF. 13 , 14 There was only one proteomic study conducted 15 in 2012 which evaluated the effect of intrathecal steroid administration on protein changes in PHN-CSF. However, the steroid’s action on PHN remains complicated since the steroid treatment has proven to be effective in the short term but not the long term of PHN.…”

“… 52 − In parallel, in the present study, the activated processes and pathways enriched in the PHN-CSF, such as coagulation, complement activation, infection and immune response, phagocytosis, and cholesterol metabolism, were similar to those in previous proteomic research investigating the plasma metabolism of the PHN patients. 14 Besides, PLG and APOA1, the verified hub proteins, are reported to be mainly derived from the bloodstream rather than the CNS. All evidence assumes that the alteration of the BBB shall take place when the PHN occurs, which would permit a crosstalk between peripheral organs and CNS.…”