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

Area of Science:

• Molecular Biology
• Neuroscience
• Dermatology

Background:

• Post-surgical pain significantly impacts patient quality of life.
• The initial molecular events driving nociceptive sensitization after surgery are not fully understood.

Purpose of the Study:

• To investigate the early molecular changes at the surgical wound edge.
• To identify key genes and signaling pathways involved in post-surgical pain development.

Main Methods:

• Longitudinal sampling of surgical wound edges.
• RNA-Sequencing (RNA-Seq) to analyze gene expression.
• Multiplex fluorescence in situ hybridization for spatial gene localization.

Main Results:

• Identified significant gene induction, including interleukin-6, oncostatin M, and leukemia inhibitory factor.
• Localized these induced factors to cutaneous structures like epidermis, hair follicles, and sweat glands.
• Demonstrated expression of factor receptors on dorsal root ganglion neurons, indicating a signaling pathway to the spinal cord.

Conclusions:

• Elucidated the inflammatory and tissue repair transcriptional landscape in human skin post-surgery.
• Provided novel insights into the molecular interactome activated by tissue injury.
• Established a link between skin injury, molecular signaling, and the initiation of post-surgical pain.