Linking Neural Anatomy to Genetics: Advancing Neuromodulation through Multi-Level Analysis

Neuromodulation, a branch of neural interfacing, is the process of altering the nervous system directly by delivering electrical impulses or chemical agents to a targeted area in the body. By modifying the transmission of information between the nerves and the brain, neuromodulation allows for the alteration of mobility and pain reception. For example, neuromodulation therapies such as Vagus Nerve Stimulation (VNS) and Spinal Cord Stimulation (SCS), can be used effectively in managing chronic pain. However, current understanding of peripheral nerve microanatomy is limited, making it difficult to design effective neural interfaces. To improve the accuracy and efficacy of computational modeling in neuromodulation therapies, a better characterization of the peripheral nerve microanatomy is necessary. A significant component of the peripheral nervous system is the sympathetic trunk, which is a target for therapeutic interventions such as sympathetic nerve blocks for pain management and specific types of neuromodulation therapies. The aim is to utilize sympathetic trunk nerves from multiple cadavers to analyze and unveil microvariations in the fascicular structures of the sympathetic trunk and contribute to the future of neuromodulation therapies. We seek to conduct the first study that uses three different antibody stains on sympathetic trunk pieces from the left and right cervical regions. Overall, results showed uneven fiber density distribution within fascicles, likely due to functional specialization. Structural variations, including differences in epineurium size, fascicle/endoneurium area, and perineurium thickness among individuals, highlight the need for personalized diagnosis and treatment. These results provide a deeper understanding of the interplay between neural anatomy and genetic factors, ultimately advancing the design of more precise neuromodulation therapies.