Exploring the bidirectional causal associations between pain and circulating inflammatory proteins: A Mendelian...

Area of Science:

• Genetics and Molecular Biology
• Immunology
• Pain Medicine

Background:

• Chronic pain, both multisite (MCP) and site-specific (SSCP), may be linked to circulating inflammatory proteins.
• The precise causal relationship between these proteins and various chronic pain conditions remains largely unknown.

Purpose of the Study:

• To investigate the potential causal relationships between 91 circulating inflammatory proteins and MCP and SSCP using Mendelian randomization.
• To identify specific inflammatory proteins that may act as protective factors or risk factors for different types of chronic pain.

Main Methods:

• A two-sample bidirectional Mendelian randomization (MR) analysis was employed.
• Data from 91 circulating inflammatory proteins, MCP, and SSCP (including headache, back, shoulder, hip, knee, abdominal, and facial pain) were analyzed.
• Inverse variance weighting was the primary MR method, supplemented by sensitivity analyses (weighted median, MR-PRESSO, Egger intercept) and heterogeneity tests (Cochrane's Q, leave-one-out).

Main Results:

• A causal relationship was established between 29 circulating inflammatory proteins and chronic pain conditions.
• Fourteen proteins demonstrated a protective effect against MCP and SSCP, while 15 proteins were identified as risk factors.
• Importantly, MCP and SSCP did not show a significant causal impact on circulating inflammatory protein levels.

Conclusions:

• Specific circulating inflammatory proteins have a causal influence on the development and progression of MCP and SSCP.
• These findings highlight potential therapeutic targets for managing chronic pain conditions.
• The study provides a foundation for developing novel treatments by modulating inflammatory protein pathways.