title: 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.
  
  
  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.
authors.affiliation: Strelitz Diabetes Institutes, Eastern Virginia Medical School, Norfolk, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Stansberry
authors.forename: H R
authors.initials: HR
authors.lastname: Peppard
authors.forename: L M
authors.initials: LM
authors.lastname: Babyak
authors.forename: G
authors.initials: G
authors.lastname: Popp
authors.forename: P M
authors.initials: PM
authors.lastname: McNitt
authors.forename: A I
authors.initials: AI
authors.lastname: Vinik
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D016022:Case-Control Studies; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000294:innervation; D005260:Female; D006197:Hair; D006225:Hand / Q000098:blood supply / Q000294:innervation; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D008955:Models, Cardiovascular; D010146:Pain / Q000473:pathology / Q000503:physiopathology*; D012039:Regional Blood Flow; D012684:Sensory Thresholds / Q000502:physiology; D012867:Skin / Q000098:blood supply* / Q000294:innervation; D014664:Vasodilation / Q000502:physiology