In the last 30 years or so, the publication of the full human genome sequence has led to the development of a new scientific field, the -omics which describe and measure all the biological molecules in an organism. It can also determine their function and how they interact in the organism. The rapid evolution of -omics approaches continues to enhance our understanding of molecular pathophysiology of pain using human cohorts, which has an obvious advantage over animal models. Omics can be achieved using molecular and cellular genome-wide approaches, in other words, scanning across different molecular and cellular sets to find a marker in cohorts that have been characterized for different pain states and different pain-related intermediate phenotypes.
Goal
The -omics approaches can be performed in human patients with pain which represent an advantage to the approaches using animal models. Animal models are still critical to the overall strategy as they allow a much wider range of mechanistic approaches to follow-up human omic studies. In this review, Luda Diatchenko and Jeffrey Mogil aimed to provide examples of -omics approaches used in their laboratories as well as animal model studies following -omics discoveries.
Methodology
Omics analyses provide a new and critical tool for pain research, contributing new information needed for the understanding of the pathophysiology of chronic pain. The list of -omics approaches to study pain is growing, and many studies are analyzing human samples at the levels of methylomics, metabolomics, lipidomics, and proteomics, promising new and exciting discoveries. These -omics studies will be also combined with other techniques in the wider context of pain research.
Genome-wide association studies (GWAS) identify genetic variants that occur at a relatively high frequency (> 1%) in the population and associates them statistically with either the presence or severity of a particular disease, in this case pain.
Transcriptome profiling for pain phenotypes is performed to measure gene expression by measuring all mRNAs expressed in a tissue (transcriptome-wide level).
Immune profiling analyzes the serological fluid in blood to find biomarkers of the immune system that can contribute to the development of pain state.
Main findings
Each -omics approach has its own strengths and limitations, and in the long term, a wide variety of -omics analyses should be used. The integration between different -omics approaches is also important. In this review, GWAS mapped genetic variants associated with chronic but not acute low back pain that were significantly enriched in nervous system related pathways such as neurogenesis and synaptic plasticity. Furthermore, GWAS results of chronic overlapping pain conditions proposed new mechanism of chronic pain development. It suggested that brain axonogenesis contributes to chronic overlapping pain conditions via corticolimbic circuits. Transcriptome profiling analysis suggested that there is an adaptive component of the immune system that protects against the transition to chronic pain, and inefficiency of these processes can lead to chronic pain. A new heuristic model of the neuroimmune interaction pathogenesis of fibromyalgia is proposed following immune profiling studies, suggesting that chronic activation and redistribution of circulating natural killer (NK) cells to the peripheral nerves contribute to the immunopathology associated with fibromyalgia.
Take home message
Results of the -omics studies suggest that chronic pain is a multistage process developing over a substantial period. Although a particular -omics analysis might identify the association with a specific immune cell type (or specific gene, or specific biological process), the overall process of pain development or resolution most likely includes multiple immune cell types. These elements might contribute to the process in a sequential manner, or they might be complementary to each other.
