Transcriptomic Profiles Associated with Experimental Placebo Effects in Chronic Pain.

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Placebo effects are a significant factor in pain management but their underlying gene expression networks are not well understood.
• Identifying molecular correlates of placebo responsivity can lead to personalized pain treatment strategies.

Purpose of the Study:

• To identify transcriptomic profiles associated with placebo responsivity in individuals with chronic pain.
• To investigate the biological processes and gene expression patterns linked to placebo effects.

Main Methods:

• Chronic pain participants underwent a conditioning paradigm to elicit placebo effects, reporting pain via a visual analog scale (VAS).
• RNA sequencing was performed on blood samples to identify differentially expressed genes (DEGs) associated with placebo effects.
• Unbiased enrichment analyses were used to determine biological pathways implicated in placebo responsivity.

Main Results:

• Out of 10,700 protein-coding genes, 667 were significantly associated with placebo effects (FDR <0.05).
• 97% of upregulated genes correlated with larger placebo effects.
• Six validated genes (CCDC85B, FBXL15, HAGH, PI3, SELENOM, TNFRSF4) showed significant positive correlation with placebo effects.
• DEGs were enriched in RNA metabolism, ribosome biogenesis, and regulation of SLITs/ROBOs, and Huntington's disease pathways.

Conclusions:

• Gene expression profiles are significantly associated with placebo responsivity in chronic pain.
• Alterations in RNA metabolism, ribosome biogenesis, and related pathways may influence an individual's susceptibility to placebo effects.
• Further research is needed to validate these findings and explore the molecular mechanisms of placebo effects in pain management.