title: Impaired skin microvascular reactivity in painful diabetic neuropathy.
abstract: OBJECTIVE
  The pathogenesis of painful diabetic neuropathy (PDN) is not clear. Following our in vivo observations of increased sural nerve epineurial blood flow in patients with PDN, we investigated the cutaneous microcirculation of the foot by laser Doppler flowmetry to determine if the epineurial findings were just confined to the nerve or more widespread in other vascular beds.
  
  
  METHODS
  We measured foot skin vasodilator responses to acetylcholine (Ach) and sodium nitroprusside (SNP) and vasoconstrictor responses to sympathetic (deepest possible gasp) stimulation in 5 healthy control subjects, 10 non-neuropathic diabetic (NND) patients, 10 diabetic patients with painless neuropathy (PLDN), and 8 diabetic patients with PDN.
  
  
  RESULTS
  In PDN, there were significantly reduced responses to Ach (ANOVA P = 0.003) and vasoconstrictor inspiratory gasp (ANOVA P < 0.001) but not to SNP (NS). Post hoc analysis showed significant differences in Ach-induced vasodilation between PDN and nondiabetic control subjects (P < 0.05) as well as between PDN and NND (P < 0.05) but not PDN and PLDN (NS). There were no significant differences for SNP-induced vasodilation. However, there were significant differences in the vasoconstrictor response between PDN and control, NND, and PLDN (P < 0.01).
  
  
  CONCLUSIONS
  We found an impairment of cutaneous endothelium-related vasodilation and C-fiber-mediated vasoconstriction in PDN. Inappropriate local blood flow regulation may have a role in the pathogenesis of pain in diabetic neuropathy. Prospective studies are required to determine the temporal relationship of these changes in relation to the emergence of neuropathic pain.
authors.affiliation: Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield S10 2JF, UK.
authors.forename: Cristian
authors.initials: C
authors.lastname: Quattrini
authors.forename: Nigel D
authors.initials: ND
authors.lastname: Harris
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
authors.forename: Solomon
authors.initials: S
authors.lastname: Tesfaye
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D005260:Female; D005528:Foot / Q000098:blood supply; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000473:pathology*; D008875:Middle Aged; D009443:Neuritis / Q000209:etiology / Q000503:physiopathology*; D009599:Nitroprusside / Q000494:pharmacology; D012016:Reference Values; D012867:Skin / Q000098:blood supply* / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D009599:Nitroprusside; D000109:Acetylcholine