Alcohol Consumption Modulates the Development of Chronic Pain in COVID-19 Patients: A Network Meta-Analysis

TL;DR

This study explores how alcohol consumption affects chronic pain in COVID-19 patients by analyzing gene expression and signaling pathways in the brain.

Contribution

The study reveals how alcohol and COVID-19 interact to influence pain signaling through shared molecular pathways in the brain.

Findings

Alcohol consumption inhibits pain-related signaling in a simulated network.

COVID-19 increases neuropathic and inflammatory pain signaling in the brain.

Shared molecules between alcohol and pain constructs were identified using gene expression data.

Abstract

The mechanisms underlying the onset and progression of
chronic
pain in COVID-19 patients have been understudied. Using network meta-analysis,
we previously demonstrated that alcohol augments COVID-19 symptoms
and pathologies possibly by inducing a severe cytokine storm. We and
others have also reported that acute alcohol consumption produces
analgesic effects, while chronic alcohol consumption results in hyperalgesia
and chronic pain. This study aimed to identify the influence of alcohol
consumption and COVID-19 on pain. Using publicly available curated
gene expression data sets of differentially expressed genes (DEGs)
in the prefrontal cortex (PFC) and amygdala of COVID-19 patients,
we employed a bioinformatics application, QIAGEN ingenuity pathway
analysis (IPA), to identify the key signaling pathways, upstream regulators,
and biological functions in these brain areas known to play a role
in pain. Canonical pathway analysis revealed activation of the neuropathic
pain pathway and signaling pathways involving the cytokine storm,
S100 family, IL-6, and neuroinflammation. IPA’s network builder
was employed to construct a network map of shared molecules between
alcohol and pain-related constructs (discomfort, neuropathic pain,
and inflammatory pain). The simulation of alcohol consumption inhibited
pain in this network map. To study the influence of COVID-19, we overlaid
the DEGs from the PFC and amygdala onto these networks, mimicking
alcohol consumption during SARS-CoV-2 infection. Upregulation of molecules
in the amygdala and PFC predicted an increase in neuropathic pain,
as well as an increase in inflammatory pain in the PFC. Our results
suggest that while alcohol consumption directly inhibits pain, the
presence of COVID-19 exaggerates impaired cytokine signaling, neuroinflammation,
and neuropathic pain signaling in the CNS providing novel insights
into the signaling pathways associated with chronic pain of the COVID-19
patients.

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