The Causal Relationship Between Immune Cells and Neuropathic Pain: A Two-Sample Mendelian Randomization Study Based on Genome-Wide Association Analysis

Wangyu Li,1 Rongguo Liu1,2 1Department of Painology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Rongguo Liu, Email [email protected]: Increasing evidence indicates that various types of immune cells are associated with different forms of neuropathic pain (NP). However, the causal relationships among these associations remain unclear. To elucidate the causal relationships between immune cells and NP, we conducted a two-sample Mendelian randomization (MR) analysis.Patients and Methods: The exposure and outcome Genome-wide association analysis (GWAS) data used in this study were obtained from open-access databases. This study employed a two-sample MR analysis to evaluate the causal relationships between 731 immune cell traits and four types of NP, including postherpetic neuralgia (PHN), trigeminal neuralgia (TN), diabetic peripheral neuropathy (DPN), and drug-induced peripheral neuropathy (DIPN).Results: The relative count of CD39+ CD4+ %T cells was positively associated with TN, while the mean fluorescence intensity (MFI) of CD20 on IgD+ CD38br (B cell) and forward scatter area (FSC-A) on myeloid dendritic cells (DCs) were negatively associated with TN. Additionally, the relative count of CD8br NKT %lymphocytes was positively associated with PHN, and the MFI of HLA DR on CD33br HLA DR+ CD14 (myeloid cells) was negatively associated with PHN. The MFI of CD4 on activated and secreting T regulatory (Treg) cells was positively associated with DPN. Furthermore, the relative count of B cell % CD3- lymphocytes was negatively associated with DIPN.Conclusion: This MR study, using genetic data from individuals of European descent, provides evidence supporting the causal relationships between several specific immune cell phenotypes and various NP subtypes.Keywords: Mendelian randomization, immune cell, neuropathic pain, causal relationship, genome-wide association analysis