Human and pig vagus nerves demonstrated comparable diameters of approximately 2 mm at the cervical level, but pig nerves contained ten times more fascicles than human nerves, whereas rat nerves were ten times smaller.
Observational (n=52)
No
Significant morphological differences exist between human, pig, and rat vagus nerves, highlighting the need to account for species-specific anatomy when designing cuff electrodes and translating preclinical vagus nerve stimulation research to clinical applications.
p-value: p=<0.0001
It is necessary to understand the morphology of the vagus nerve (VN) to design and deliver effective and selective vagus nerve stimulation (VNS) because nerve morphology influences fiber responses to electrical stimulation. Specifically, nerve diameter (and thus, electrode-fiber distance), fascicle diameter, fascicular organization, and perineurium thickness all significantly affect the responses of nerve fibers to electrical signals delivered through a cuff electrode. We quantified the morphology of cervical and subdiaphragmatic VNs in humans, pigs, and rats: effective nerve diameter, number of fascicles, effective fascicle diameters, proportions of endoneurial, perineurial, and epineurial tissues, and perineurium thickness. The human and pig VNs were comparable sizes (∼2 mm cervically; ∼1.6 mm subdiaphragmatically), while the rat nerves were ten times smaller. The pig nerves had ten times more fascicles-and the fascicles were smaller-than in human nerves (47 vs. 7 fascicles cervically; 38 vs. 5 fascicles subdiaphragmatically). Comparing the cervical to the subdiaphragmatic VNs, the nerves and fascicles were larger at the cervical level for all species and there were more fascicles for pigs. Human morphology generally exhibited greater variability across samples than pigs and rats. A prior study of human somatic nerves indicated that the ratio of perineurium thickness to fascicle diameter was approximately constant across fascicle diameters. However, our data found thicker human and pig VN perineurium than those prior data: the VNs had thicker perineurium for larger fascicles and thicker perineurium normalized by fascicle diameter for smaller fascicles. Understanding these differences in VN morphology between preclinical models and the clinical target, as well as the variability across individuals of a species, is essential for designing suitable cuff electrodes and stimulation parameters and for informing translation of preclinical results to clinical application to advance the therapeutic efficacy of VNS.
Pelot et al. (Wed,) conducted a observational in Vagus nerve morphology (n=52). Species (Human, Pig, Rat) was evaluated on Effective nerve diameter and number of fascicles (p=<0.0001). Human and pig vagus nerves demonstrated comparable diameters of approximately 2 mm at the cervical level, but pig nerves contained ten times more fascicles than human nerves, whereas rat nerves were ten times smaller.