Human pain transcriptomics: lessons learned so far

Chronic pain is currently being viewed as a major public health epidemic, especially as there is a higher rate of chronic pain amongst US adults than for other chronic diseases like diabetes, depression, and hypertension. A better understanding of the mechanisms driving chronic pain is needed to develop new and effective analgesics. Animal models have traditionally been valuable tools in pain research, but there have been many setbacks in translating preclinical findings into new therapeutics. This has brought a new sense of urgency for a better understanding of chronic pain pathophysiology in humans. To address this gap, a comprehensive and systematic study of human nociceptive pathways, integrating molecular, cellular, and systems-level data is critical for identifying clinically relevant targets and improving translational success in pain therapeutics. Fortunately, this mission has currently been aided by current advances in the next-generation sequencing coupled with the increased availability of nociceptive tissues from patients with chronic pain. As such, we and others have just begun initial studies examining the transcriptomic changes occurring in the dorsal root ganglia of subjects with chronic pain. Transcriptomic analyses of dorsal root ganglia have so far examined painful conditions including radicular/neuropathic pain, diabetic painful neuropathy, and rheumatoid arthritis. Here, we describe what has been learned from these transcriptomic studies so far, which shows that additional multiomics-driven research is needed to fully understand and target human nociceptive processes.