Anodal Current Intensities above 40 μA Interfere with Current-Induced Axon-Reflex Vasodilatation in Human Skin

Abstract

When using iontophoresis, the ‘non-specific’ vasodilatation (NSV) that is observed as a result of C-fibre excitation is generally attributed to the local accumulation of protons under the anode. NSV following prolonged 100-µA anodal current application only appears after the current is stopped. Break excitation alone does not explain the delayed onset of this vasodilatation. We hypothesised that this delay could result from an anodal block and thus, that a minimal intensity would be required to achieve hyperpolarisation of primary afferent fibres (mainly C-fibres). Using laser Doppler flowmetry, cutaneous blood flow was recorded in the forearms of 8 healthy volunteers 2 min before current application, during the application and 20 min after stopping the monopolar anodal current. In protocol 1, after 2.5 min of current application at an intensity of 100 µA, the intensity was abruptly decreased to 0–80 µA for a second 2.5-min period. The onset of vasodilatation was only delayed at intensities >30 µA during this second period. In protocol 2, re-application of the current after a 50-second interruption (expected to allow for the occurrence of an axon reflex) did not interfere with the onset of vasodilatation. Thus: (1) the minimal intensity interfering with the axon reflex is far lower than that reported for C-fibre blockade in isolated nerves; (2) the results suggest that current application does not directly interfere with the vasodilator mechanisms induced by the axon reflex at the level of smooth muscle cells.

Noninvasive Measure of Microvascular Nitric Oxide Function in Humans Using Very Low‐Frequency Cutaneous Laser Doppler Flow Spectra

“…However, Berghoff et al, using iontophoretic administration of acetylcholine [ 18 ], showed at most a 20% reduction in the response to acetylcholine. Also, a substantial fraction of the neurogenic response can be ascribed to anodal current delivered during iontophoretic drug delivery [ 17 ]. These effects are obviated in the present study by the use of drug administration through microdialysis catheters.…”

“…One might infer that it represents contributions to LDF oscillations arising from local mechanisms that may be endothelial mediated. Support for endothelial dependence of the very low‐frequency LDF oscillations originates with the work of Kvernmo using acetylcholine iontophoresis [ 14 , 15 ], although data were not definitive in untrained control subjects and were potentially confounded by the vasodilator properties of anodal current [ 16 ], which evokes a C‐fiber‐dependent axon reflex [ 17 ]. Also, acetylcholine‐dependent microvascular vasodilation in diverse tissues is axon reflex dependent [ 18 ] and may relate to other signaling molecules (e.g., prostaglandins [ 19 ] and endothelial‐dependent hyperpolarizing factor, EDHF, [ 20 ]).…”

Thermal dysregulation in patients with multiple sclerosis during SARS-CoV-2 infection. The potential therapeutic role of exercise

“…Regardless of being a frequent complaint in patients with MS, our understanding of how increases or decreases in body temperature contribute to worsening of MS symptoms is incomplete. However, as depicted in Figure 1 , the most likely mechanisms underlying heat sensitivity and the exacerbation of the symptoms of MS can be summarized as follow: Demyelinated axons in brain lesions and peripheral neurons overexpress voltage-gated Na + (Na v ) channels, particularly α-subunits, throughout their length ( Smith, 2007 ; Tartas et al, 2004 ). There have been generally revealed 9 isoforms of this type of Na v channels (Na v 1.1 to 1.9).…”

Effects of Hyperpolarization-Activated Channel Blocker ZD7288 on Polar Excitations of Frog Sciatic Nerve

“…The underlying mechanism of polar excitations has been mainly described from the properties of Na channels [1][2][3]. Although recent studies revisiting the mechanisms of polar excitations have proposed alternative models to the one initially described by Hodgkin and Huxley [4][5][6][7], none have suggested a contribution of ionic channels other than Na + or K + channels to the generation of polar excitation.…”

“…The terminal of the stimulation triggers another action potential (equal to AE) as an off-response, because the membrane potential shifts in the depolarizing direction by breaking the stimulation. A scant few reports have revisited the mechanisms of polar excitations [4][5][6][7], but none has suggested a contribution of different ionic channels other than Na + and K + channels.…”