Causal interplay between trigeminal neuralgia and systemic inflammatory markers: A bidirectional Mendelian...

Area of Science:

• Immunology
• Neurology
• Genetics

Background:

• Trigeminal neuralgia (TN) is a debilitating neuropathic pain disorder impacting quality of life.
• Previous studies on circulating inflammatory proteins in TN have yielded inconsistent findings, with limitations in establishing causality.
• Robust causal inference methods are needed to clarify the relationship between immune factors and TN.

Purpose of the Study:

• To investigate the causal relationships between circulating inflammatory proteins and trigeminal neuralgia (TN) using a bidirectional Mendelian randomization approach.
• To determine if immune system alterations are a cause or consequence of TN.
• To identify potential biomarkers and therapeutic targets for TN.

Main Methods:

• A bidirectional 2-sample Mendelian randomization (MR) analysis was performed.
• Genetic instruments for 91 circulating inflammatory proteins and TN were obtained from large-scale genome-wide association studies.
• Five complementary MR estimators and sensitivity analyses were employed to assess robustness and rule out pleiotropy.

Main Results:

• Forward MR identified five proteins associated with TN risk: eotaxin, C-X-C motif chemokine ligand 5 (CXCL5), IL-20RA, interleukin-6, and neurturin.
• Reverse MR indicated that TN causally influences five immune traits: eotaxin, CXCL5, IL-20RA, interleukin-15 receptor α, and transforming growth factor-α.
• Eotaxin, CXCL5, and IL-20RA exhibited significant bidirectional associations with TN, suggesting a coupled relationship.

Conclusions:

• Genetic evidence strongly supports a causal link between specific circulating inflammatory proteins and trigeminal neuralgia.
• The findings highlight a close coupling between the inflammatory network and TN, suggesting immune dysregulation plays a role in the disorder.
• These results provide a foundation for developing novel biomarkers and immunomodulatory treatment strategies for TN.