Priming of central- and peripheral mechanisms with heat and cutaneous capsaicin facilitates secondary hyperalgesia to high frequency electrical stimulation

Author(s):  
Rosa Hugosdottir ◽  
Mindy Kasting ◽  
Carsten Dahl Mørch ◽  
Ole Kæseler Andersen ◽  
Lars Arendt-Nielsen

Heat/capsaicin sensitization and electrical high frequency stimulation (HFS) are well known model of secondary hyperalgesia, a phenomenon related to chronic pain conditions. This study investigated whether priming with heat/capsaicin would facilitate hyperalgesia to HFS in healthy subjects. Heat/capsaicin priming consisted of a 45 °C heat stimulation for 5 min followed by a topical capsaicin patch (4x4 cm) for 30 minutes on the volar forearm of 20 subjects. HFS (100 Hz, 5 times 1s, minimum 1.5 mA) was subsequently delivered through a transcutaneous pin electrode approximately 1.5 cm proximal to the heat/capsaicin application. Two sessions were applied in a crossover design; traditional HFS (HFS) and heat/capsaicin sensitization followed by HFS (HFS+HEAT/CAPS). Heat pain threshold (HPT), mechanical pain sensitivity (MPS) and superficial blood perfusion were assessed at baseline, after capsaicin removal, and up to 40 min after HFS. MPS was assessed with pinprick stimulation (128 mN and 256 mN) in the area adjacent to both HFS and heat/capsaicin, distal but adjacent to heat/capsaicin and in a distal control area. HPT was assessed in the area of heat/capsaicin. Higher sensitivity to 128 mN pinprick stimulation (difference from baseline and control area) was observed in the HFS+HEAT/CAPS session than in the HFS session 20 and 30 minutes after HFS. Furthermore, sensitivity was increased after HFS+HEAT/CAPS compared to after heat/capsaicin in the area adjacent to both paradigms, but not in the area distal to heat/capsaicin. Results indicate that heat/capsaicin causes priming of the central- and peripheral nervous system, which facilitates secondary mechanical hyperalgesia to HFS.

2020 ◽  
Vol 24 (8) ◽  
pp. 1585-1597
Author(s):  
Timothée Cayrol ◽  
Julien Lebleu ◽  
André Mouraux ◽  
Nathalie Roussel ◽  
Laurent Pitance ◽  
...  

2020 ◽  
Vol 44 (3) ◽  
pp. 241-249
Author(s):  
Yoshiaki Omura

While a visiting Professor at the University of Paris, VI (formerly Sorvonne) more than 40 years ago, the Author became very good friends with Dr. Paul Nogier who periodically gave seminars and workshops in Paris. After the author diagnosed his cervical problem & offered him simple help, Dr. Nogier asked the Author to present lectures and demonstrations on the effects of ear stimulation, namely the effects of acupuncture & electrical stimulation of the ear lobules. It is only now, in 2019 that we have discovered 2–5 minute high frequency stimulation of the ear lobule inhibits cancer activity for 1– 4 hours post stimulation. Although the procedure is extremely simple. First take optimal dose of Vitamin D3, which has the most essential 10 unique beneficial factors required for every human cell activity. Next, apply high frequency stimulation to ear lobule while the worst ear lobule is held by all fingers with vibrator directly touching the surface of the worst ear lobule, preferably after patient repeatedly takes optimal dose of Vitamin D3. When the worst ear lobule is held between thumb & index fingers and applying mechanical stimulation of 250 ~ 500 mechanical vibration/second for 2 ~ 5 minutes using an electrical vibrator, there is rapid disappearance of cancer activity in both the brain and rest of the body for short time duration 1 ~ 4 hours. The effect often increases by additional pressure by holding fingers. As of May 2019, the Author found that many people from various regions of the world developed early stages of multiple cancers. For evaluation of this study, U. S. patented Bi-Digital O-Ring Test (BDORT) was used which was developed by the Author while doing his Graduate experimental physics research at Colombia University. BDORT was found to be most essential for determining the beneficial effects as well as harmful effects of any substance or treatment. Using BDORT, Author was the first to recognize severe increasing mid-backache was an early sign of pancreatic cancer of President of New York State Board of Medicine after top pain specialists failed to detect the cause after 3 years of effort, while the BDORT showed early stages of cancer whereas conventional X-Ray of the pancreas did not show any cancer image until 2 months after Author detected with BDORT. For example, the optimal dose of the banana is usually about 2.0 - 2.5 millimeters cross section of the banana. A whole banana is more than 50 ~ 100 times the optimal dose. Any substance eaten in more than 25 times of its optimal dose becomes highly toxic and creates DNA mutations which can cause multiple malignancies in the presence of strong electro-magnetic field. With standard medication given by doctor, patients often become sick and they are unable to reduce body weight, unless medication is reduced or completely stopped. When the amount of zinc is very high, DNA often becomes unstable and multiple cancers can grow rapidly in the presence of strong electromagnetic field. Large amount of Vitamin C from regular orange or orange juice inhibit the most important Vitamin D3 effects. At least 3 kinds of low Vitamin C oranges will not inhibit Vitamin D3. Since B12 particularly methyl cobalamin which is a red small tablet is known to improve brain circulation very significantly we examined its effect within 20 seconds of oral intake we found the following very significant changes. Acetylcholine in both sides of the brain often increases over 4,500 ng. Longevity gene Sirtuin 1 level increases significantly for short time of few hours. Thymosin α1 and Thymosinβ4 both increase to over 1500 ng from 20 ng or less.


1957 ◽  
Vol 40 (3) ◽  
pp. 435-450 ◽  
Author(s):  
David P. C. Lloyd

An assemblage of individual motoneurons constituting a synthetic motoneuron pool has been studied from the standpoint of relating monosynaptic reflex responses to frequency of afferent stimulation. Intensity of low frequency depression is not a simple function of transmitter potentiality. As frequency of stimulation increases from 3 per minute to 10 per second, low frequency depression increases in magnitude. Between 10 and approximately 60 per second low frequency depression apparently diminishes and subnormality becomes a factor in causing depression. At frequencies above 60 per second temporal summation occurs, but subnormality limits the degree of response attainable by summation. At low stimulation frequencies rhythm is determined by stimulation frequency. Interruptions of rhythmic firing depend solely upon temporal fluctuation of excitability. At high frequency of stimulation rhythm is determined by subnormality rather than inherent rhythmicity, and excitability fluctuation leads to instability of response rhythm. In short, whatever the stimulation frequency, random excitability fluctuation is the factor disrupting rhythmic response. Monosynaptic reflex response latency is stable during high frequency stimulation as it is in low frequency stimulation provided a significant extrinsic source of random bombardment is not present. In the presence of powerful random bombardment discharge may become random with respect to monosynaptic afferent excitation provided the latter is feeble. When this occurs it does so equally at low frequency and high frequency. Thus temporal summation is not a necessary factor. There is, then, no remaining evidence to suggest that the agency for temporal summation in the monosynaptic system becomes a transmitting agency in its own right.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H.I Condori Leandro ◽  
N Goncharova ◽  
A Vakhrushev ◽  
L Korobchenko ◽  
E Andreeva ◽  
...  

Abstract Introduction Pulmonary artery denervation (PAD) has been recently shown to decrease pulmonary artery (PA) pressure. However, there is a lack of data related to target sites for ablation. Purpose To determine the optimal PA ablation sites based on response to high-frequency stimulation mapping and anatomical areas where radiofrequency ablation (RFA) should be avoided due to the risk of severe collateral damage. Methods A total of 17 Landrace swines were included into the study. PA angiography, hemodynamic measurements by right heart-sided catheterization and electrophysiological mapping (EM) using low (cycle length 330 ms) and high-frequency (33Hz) stimulation (HFS). Stimulation was performed at PA bifurcation and proximal parts of the main PA branches with a 5-mm distance between points; catheter manipulation was performed under fluoroscopic guidance in multiple projections. Points with evoked reactions were tagged on a 3-dimentional PA model in each case. In order to confirm reproducibility of reactions, HFS was performed at least twice at each point with a response. PA models obtained from all animals were combined in one for the final analysis. RFA using an open-irrigated catheter (40 Watts; 40 s; irrigation 30 ml/min) were performed at sites with evoked reactions. Repeated HFS was performed at ablation sites. After the procedure all animals were euthanized and underwent an autopsy study. Results Low-frequency stimulation (LFS) allowed to define areas of ventricular capture (VC) where HFS was avoided due to ventricular fibrillation induction risk. During HFS the following evoked responses were documented: sinus bradycardia, sinus rhythm (SR) acceleration, phrenic nerve capture (PNC), and laryngeal recurrent nerve capture. HFS captured left and right phrenic nerves in all animals at PA trunk, and its course was tagged (Figure 1). Laryngeal recurrent nerve capture was found in 4 (23%) of animals. Atrial capture was found in all cases while LFS at the anterior aspects of both PAs even at low output, and this precluded evaluation of neural autonomic reactions in these areas. Evoked bradycardia and SR acceleration were both found during HFS in 10 (59%) of cases each. Following RFA application evoked reactions were non-reproducible in all cases. RFA was applied in areas where no PNC or VC points were observed. An autopsy study confirmed the presence of RF-induced lesions of the PA wall. Conclusions There are two important findings of our study. First, stimulation-guided PA mapping is feasible and reveals several specific responses to HFS. Ablation at points with responses leads to non-reproducibility of the evoked reactions, confirming that transcatheter RFA may be an adequate approach for PA denervation. Second, previously proposed circular PA ablation might be associated with phrenic and laryngeal recurrent nerve damage. Stimulation-guided PA denervation can be proposed as a safer procedure, and should be evaluated in clinical settings. Figure 1. PA schematic representation Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Russian Foundation for Basic Research


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Musa Ozturk ◽  
Ashwin Viswanathan ◽  
Sameer A. Sheth ◽  
Nuri F. Ince

AbstractDespite having remarkable utility in treating movement disorders, the lack of understanding of the underlying mechanisms of high-frequency deep brain stimulation (DBS) is a main challenge in choosing personalized stimulation parameters. Here we investigate the modulations in local field potentials induced by electrical stimulation of the subthalamic nucleus (STN) at therapeutic and non-therapeutic frequencies in Parkinson’s disease patients undergoing DBS surgery. We find that therapeutic high-frequency stimulation (130–180 Hz) induces high-frequency oscillations (~300 Hz, HFO) similar to those observed with pharmacological treatment. Along with HFOs, we also observed evoked compound activity (ECA) after each stimulation pulse. While ECA was observed in both therapeutic and non-therapeutic (20 Hz) stimulation, the HFOs were induced only with therapeutic frequencies, and the associated ECA were significantly more resonant. The relative degree of enhancement in the HFO power was related to the interaction of stimulation pulse with the phase of ECA. We propose that high-frequency STN-DBS tunes the neural oscillations to their healthy/treated state, similar to pharmacological treatment, and the stimulation frequency to maximize these oscillations can be inferred from the phase of ECA waveforms of individual subjects. The induced HFOs can, therefore, be utilized as a marker of successful re-calibration of the dysfunctional circuit generating PD symptoms.


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