In this immunohistochemical study we investigated the expression of lo
w-affinity NGF receptor (p75(NGFR)) in peripheral nerves from 16 patie
nts with type I or type II diabetes mellitus. Fourteen nerves from age
-and sex-matched normal individuals and nine nerves from non-diabetic
patients with ischemic neuropathy served as controls. All nerve sample
s were preliminarily examined by standard histology, fiber teasing and
electron microscopy. Increased p75(NGFR) immunoreactivity was detecta
ble within the endoneurium of cross-sections from ischemic and particu
larly from diabetic nerves. Immune-teasing demonstrated that p75(NGFR)
immunostaining was distributed along the entire length of isolated ne
rve fibers undergoing axonal degeneration. Quantitative assessment of
p75(NGFR) immunoreactivity, performed by histospectrophotometry and ex
pressed as percentage of adsorbance, was 21.20 +/- 3.50 in nerves from
diabetic patients, 13.35 +/- 3.62 in nerves from non-diabetic patient
s with ischemic neuropathy and 9.02 +/- 2.75 in normal controls. The i
ncreased expression of p75(NGFR) in diabetic nerves is consistent with
an axonopathic defect and further suggests involvement of NGF and oth
er neurotrophins in the pathogenesis of human diabetic neuropathy.