Quantitative assessment of the innervation of epineural arteries in the peripheral nerve by immunofluorescence: Differences between controls and patients with peripheral arterial disease

The peripheral nerve is supplied by the vasa nervorum. The epi- and perineurial vessels are innervated by an autonomic plexus, which plays a role in regulation of the endoneurial blood flow. This innervation is decreased in diabetes and alcohol polyneuropathy and seems to precede the development of diabetic polyneuropathy. A decreased innervation may therefore play a role in the development of polyneuropathy. In peripheral arterial disease (PAD) clinical and morphological features are present, related to severity of ischemia. To investigate the innervation of the vasa nervorum in severe ischemia, we performed immunofluorescence staining with the general neural marker protein gene product (PGP) 9.5 in whole mount preparations of epineurial vessels of nine sural nerves taken from patients with legs amputated because of severe PAD (59±15 years, mean ± SD) and ten age-matched controls (61±24 years). In patients with PAD the nerve density of the perivascular plexus was decreased in comparison with controls (mean intercept density/mm ± SD) 26.0±6.9 in PAD and 39.9±10.7 in controls, area % 6.0± 1.6 in PAD and 9.9±2.6 in controls, both P<0.01, t-test). A decreased perivascular plexus may result in a diminished regulation of the endoneurial blood flow in patients with severe PAD.