Beyond Neuroimaging: A Bottom-Up Approach to Unraveling Pain Mechanisms in the Brain

A deeper understanding of pain signaling pathways is necessary to help improve analgesics, which are often unsuccessful in managing pain. Top-down neuroimaging studies have identified patterns of cerebral structures activated by painful stimuli; however, they tend to oversimplify the complexity of pain processing in the brain. Our study takes a novel, bottom-up approach, focusing on the dorsal horn transcriptome, offering a comprehensive exploration of the initial integration point of nociceptive signals, to identify brain areas of similar genetic composition to unravel mechanisms underlying acute and chronic pain. Data from the Human Protein Atlas underwent transcriptomic analyses using R to determine dorsal horn enriched genes. Gene set enrichment analysis referenced the Allen Brain Atlas to determine a structure of similar genetic composition. The region was delineated using MRI scans (N=50; Age:27.6±6.4 years) to determine structural characteristics. Functional characteristics will be determined by analyzing local variances in blood flow using arterial spin labeling. Pain ratings were obtained by laser stimulus. The genetic fingerprint of the dorsal horn was mapped to the Bed Nuclei of the Stria Terminalis (BNST). We found a significant negative correlation between BNST volume and perceived pain ratings (Pearon’s r=-0.3, p.adj=0.0153). The BNST is not well studied in the context of pain, with only a few studies analyzing its properties in animal models. Our results indicate its potential involvement in pain processing in humans. Future analyses will analyze functional determinants of the BNST in relation to acute pain sensitivity and morphological differences between healthy and chronic pain subjects.