Papers of the Week

A growing body of evidence suggests a correlation among immune cells, serum micronutrient levels, and neuropathic pain. However, previous studies have been limited in scope, hindering the establishment of conclusive findings. Therefore, this study employs mendelian randomization (MR) analysis to investigate the genetic perspectives on the causal relationships among these factors. Initially, the relationship between five serum micronutrient levels (specifically, four vitamin levels and zinc levels) and neuropathic pain was examined using a bidirectional MR design. Subsequently, positive results identified through the inverse variance weighted (IVW) method prompted further analysis, using immune cells as exposures to explore their causal links with neuropathic pain. As a result, a two-step MR analysis demonstrated that serum vitamin levels mediate the relationship between immune cells and neuropathic pain, quantifying both direct impacts and mediation effects. This study revealed that low serum levels of vitamin D and 25-hydroxyvitamin D increased the risk of postherpetic neuralgia and thoracic spine pain. Reverse MR analysis suggested that neuropathic pain does not contribute to a reduction in the serum levels of vitamin D and 25-hydroxyvitamin D. Furthermore, significant associations were observed between 27 immune cells and postherpetic neuralgia, as well as between 22 immune cells and thoracic spine pain. Additionally, the mediation analysis identified causal relationships between immune cells and serum micronutrient levels, confirming the “immune cells-serum micronutrient levels-neuropathic pain” pathway. This study provides valuable insights into the potential mechanisms by which vitamin D and 25-hydroxyvitamin D regulate the interaction between the immune system and neuropathic pain. These findings are crucial for the timely detection, treatment, and management of neuropathic pain, offering new perspectives on how vitamin levels influence immune cell behavior and neuropathic pain susceptibility.