OBJECTIVE - To examine whether changes in circulating norepinephrine a
re associated with the sensory disturbances of diabetic polyneuropathy
. Experimental studies have indicated that NE can excite sprouts from
injured nerves, producing pain. RESEARCH DESIGN AND METHODS- We measur
ed supine and erect plasma NE in 13 normal, nondiabetic control subjec
ts and three groups of diabetic patients: 20 without clinical neuropat
hy, 20 with chronic painful neuropathy, and 15 with painless neuropath
y and foot ulceration. Neuropathy was characterized by symptom and def
icit scores, sensory thresholds, electrophysiology, and cardiovascular
autonomic function tests. Neuropathic pain was scored by the patients
on a linear analogue scale. RESULTS- In painless neuropathy, NE level
s were greatly reduced (supine, 1.3 nM; erect, 2.2 nM) compared with c
ontrol subjects (supine, 2.4 nM; erect, 4.0 nM; P < 0.001) and were co
mbined with grossly abnormal autonomic reflexes. NE also was reduced i
n the diabetic group without neuropathy (supine, 1.7 nM; erect, 2.7 nM
; P < 0.01 vs. control subjects). By contrast, in painful neuropathy N
E levels (supine, 2.2 nM; erect, 3.6 nM) were similar to control subje
cts and significantly higher than in painless neuropathy (P < 0.01). F
urthermore, NE correlated with the severity of neuropathic pain (r = 0
.46, P = 0.02). To assess whether pain, acting as a stressor, could ac
count for the observed differences in NE, we also measured the stress
hormones epinephrine and cortisol. They did not differ among the diabe
tic groups. CONCLUSIONS- Circulating NE is higher in painful than pain
less diabetic neuropathy. We suggest that painful neuropathy is associ
ated with a relatively higher number of functioning sympathetic fibers
that may contribute to pain.