PROJECT SUMMARY Chronic pain is complex, diverse, and difficult to manage, and current treatments, such as opioids, are not effective for many individuals. The genes, circuits, and cells regulating chronic pain remain a black box. In particular, research on how the genes, circuits, and cells regulating chronic pain change across the lifespan in vulnerable populations including infants, children, elders, pregnant women is understudied and often ignored. The knowledge gap in understanding the underlying mechanisms of chronic pain is mainly due to the lack of innovative technologies to map and decode the pain-associated genes, circuits, and cells at high resolution and scale. We will develop novel single-cell technologies “Raman2Omics” that are highly modular and broadly applicable to map the genes, circuits, and cells associated with pain. We will utilize a mouse model of postoperative pain to investigate the underlying molecular mechanisms across ages, sexes, and during pregnancy. We will apply “Raman2Omics” to systematically investigate genes and cells associated with postoperative pain at scale. With these innovative single-cell technologies, we will be able to generate highly valuable molecular information and identify novel candidate biomarkers and therapeutic targets for chronic pain, which will lead to the development of novel diagnosis and treatment solutions. Meanwhile, “Raman2Omics” can be readily applied to investigate other multicellular complex tissues in health and diseases.

PROJECT NARRATIVE The genes, circuits, and cells regulating chronic pain across the lifespan in vulnerable populations remain a black box. We aim to develop novel experimental and computational single-cell technologies to decode the pain- associated genes and cells at scale.