Longitudinal human transcriptomic and spatial gene profiling at the incisional edge during long surgical procedures.

Post-surgical pain remains a widespread problem reducing quality of life. The present study investigates the initial molecular changes underlying nociceptive sensitization through longitudinal, temporal sampling at the surgical wound edge. Using RNA-Seq and multiplex fluorescence in situ hybridization, we examined the most significant genes induced by tissue injury including those coding for the secreted factors interleukin 6, oncostatin M and leukemia inhibitory factor, and localized these induction events to several cutaneous structures including the epidermis, vascular endothelia, hair follicles, and sweat glands. Our data also demonstrate the receptors for these key secreted factors are expressed by dorsal root ganglion neurons, indicating long-range signaling from damaged skin to spinal cord, thereby leading to pain. This study provides a novel understanding of tissue structures and the molecular interactome activated following tissue injury by elucidating the inflammatory and tissue repair transcriptional milieu induced by surgery in human skin excision biopsies.