Primary nociceptive afferents mediate the blood flow dysfunction in non-glabrous (hairy) skin of type 2 diabetes: a new model for the pathogenesis of microvascular dysfunction.

Abstract

OBJECTIVE: To test the independent contributions of vascular endothelium, sympathetic activation and inhibition, vessel distensibility, and nociceptor-mediated vasodilation in both glabrous and hairy skin circulations. RESEARCH DESIGN AND METHODS: We measured blood flow using laser Doppler techniques in 10 people with type 2 diabetes and 10 age- and BMI-matched healthy control subjects at the pulp of the index finger (glabrous skin) and the dorsum of the hand (hairy skin). A 5-min ischemic block of the arm was used to test vascular endothelium. Warming of the probe site to 45 degrees C tested neurogenic vasodilation in hairy skin only. Vessel distensibility was tested by gravitational pressure. RESULTS: Basal blood flow and reactive hyperemia did not differ between groups at either skin site. The vasodilative response to local warming (P < 0.01) and limb lowering (P < 0.05) were significantly different between groups in hairy skin but not in glabrous skin in the absence of objective measured neuropathy. Nociceptor-mediated flow correlated significantly with the warm thermal threshold (r = -0.50, P < 0.05). Endothelial-mediated blood flow correlated with systolic blood pressure (r = -0.76, P < 0.01), LDL cholesterol (r = -0.62, P < 0.001), C-peptide (r = 0.65, P < 0.05), and triglycerides (r = 0.47, P < 0.05). CONCLUSIONS: These data suggest that neurogenic nociceptor-mediated vasodilation is impaired in subjects with type 2 diabetes when endothelial and sympathetic function are relatively intact. Heat-induced vasodilation may be a specific test of small heat-sensitive C-fiber peripheral neurons and may be an integral part of the metabolic syndrome.