Neurovascular microcirculatory vasodilation mediated by C-fibers and Transient receptor potential vanilloid-type-1 channels (TRPV 1) is impaired in type 1 diabetes

Abstract

Microvascular dysfunction may have an early onset in type 1 diabetes (T1D) and can precede major complications. Our objectives were to assess the endothelial-dependent (acetylcholine, ACh; and post-occlusive hyperemia, PORH), non-endothelial-dependent (sodium nitroprusside, SNP) and neurovascular-dependent (local heating, LH and current induced vasodilation, CIV) microcirculatory vasodilation in T1D patients compared with matched control subjects using a laser speckle contrast imager. Seventeen T1D patients - matched with 17 subjects according to age, gender, Body-Mass-Index, and smoking status - underwent macro- and microvascular investigations. The LH early peak assessed the transient receptor potential vanilloid type 1 channels (TRPV1) mediated vasodilation, whereas the plateau assessed the Nitirc-Oxyde (NO) and endothelium-derived hyperpolarizing factor (EDHF) pathways. PORH explored sensory nerves and (EDHF), while CIV assessed sensory nerves (C-fibers) and prostaglandin-mediated vasodilation. Using neurological investigations, we observed that C-fiber and A-delta fiber functions in T1D patients were similar to control subjects. PORH, CIV, LH peak and plateau vasodilations were significantly decreased in T1D patients compared to controls, whereas there was no difference between the two groups for ACh and SNP vasodilations. Neurovascular microcirculatory vasodilations (C-fibers and TRPV 1-mediated vasodilations) are impaired in TD1 patients whereas no abnormalities were found using clinical neurological investigations. Clinicaltrials: No. NCT02538120.

The role of C-afferents in mediating neurogenic vasodilatation in plantar skin after acute sciatic nerve injury in rats

“…These studies suggest that sensory nerves may play a more important role in regulating cutaneous vasomotor activity than expected. Recent studies in humans also suggest that C-afferents play a role in mediating neurogenic vasodilation that is impaired in diabetes patients and in aged human skin [27][28][29]. In the present study we found, by using nerve deafferentation and C-afferentspecific stimulation models, that C-fiber afferents are predominantly responsible for neurogenic vasodilatation following traumatic nerve injury in the glabrous skin.…”

<p>Advances with Long Non-Coding RNAs in Diabetic Peripheral Neuropathy</p>

“…19 Several of these studies have shown that activation of transient receptor potential vanilloid type 1 (TRPV1) in neurons plays an important role in peripheral neuralgia caused by diabetes. [20][21][22] A research showed that in the streptozotocin-induced diabetic rat model, lncRNA BC168687 siRNA increased the thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) of diabetic rats and alleviated DPN by regulating transient receptor potential vanilloid type 1 (TRPV1) and cytokines (TNF-α and IL-1β). 23 The production of TNF-α and IL-1β and other inflammatory factors is closely related to the activation of ERK (extracellular regulated protein kinases) and p38 pathways.…”

Die Rolle der diabetischen Neuropathie bei der Genese des Charcot-Fußes

“…Als nozizeptive Sensoren der C-und Aδ-Fasern gelten unter anderem die Transient Receptor Potenzial (TRP) Kanäle, zu deren aktivierenden und sensitivierenden Faktoren Hitze oder Kälte, Protonen, reaktive Sauerstoffspezies, Stickstoffmonoxid sowie intrazelluläre Modulationswege zählen [38]. TRPV1-Kanäle aus C-Fasern sind gleichzeitig auch verantwortlich für die Peak-Vasodilatation nach Ischämie oder Stauung [39].…”