PLASMA NOREPINEPHRINE IN SENSORY DIABETIC POLYNEUROPATHY

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.