Reconstruction of the Pathophysiology of Chronic Pain from Genome-wide Studies
Luda Diatchenko, M.D., Ph.D.
Canada Excellence Research Chair in Human Pain Genetics
Pfizer Canada Professor in Pain Research
The Diatchenko lab investigates the psychological, molecular, cellular, and genetic pathways that mediate both acute and persistent pain states. Their primary goal is to identify the critical elements of human genetic variability contributing to pain sensitivity and pathophysiological pain states that will enable individualized treatments and therapies. Other related research endeavors include molecular hierarchy of functional SNPs (single-nucleotide polymorphisms) and SNP-depend regulation of gene expression, underlying molecular pain signaling. Answering these questions requires collaboration with experts in both clinical and basic biological sciences. Such collaborative activities allow the Diatchenko group to take basic genetic findings all the way from human association studies, through molecular and cellular mechanisms, to animal models, and ultimately to human clinical trials.
The molecular pathophysiology of chronic pain is largely unknown. The genetic and molecular studies of human pain can nevertheless provide critical insights into pathophysiological mechanisms of pain “chronification,” the process of transient pain progressing into persistent pain. Genome-wide “omics” approaches allow a whole human genome scan that is hypothesis-free and permit systematic use and integration of multiple genome-wide datasets, resulting in unbiased interpretation of data. In this talk, Dr. Diatchenko will describe three examples of how genome-wide genetic profiling, immune profiling, and transcriptome-wide profiling provide new and unexpected insights into human chronic pain molecular pathophysiology. She will discuss how these approaches identified substantial shared genetic heritability between different chronic pain conditions driven by netrin-dependent axonal guidance projection, a natural killer cell-peripheral nerve axis in fibromyalgia, and how acute inflammatory response via neutrophil activation protects against pain chronification.
This page was last updated on Wednesday, May 18, 2022