scholarly journals Heterosynaptic facilitation of mechanical nociceptive input is dependent on the frequency of conditioning stimulation

2019 ◽  
Vol 122 (3) ◽  
pp. 994-1001 ◽  
Author(s):  
E. N. van den Broeke ◽  
S. Gousset ◽  
J. Bouvy ◽  
A. Stouffs ◽  
L. Lebrun ◽  
...  
Keyword(s):  
Human Skin ◽  
High Frequency ◽  
Receptor Activation ◽  
High Frequency Stimulation ◽  
Secondary Hyperalgesia ◽  
Conditioning Stimulation ◽  
Maximal Increase ◽  
Significant Difference ◽  
Neurokinin 1 ◽  
Electrical Conditioning

High-frequency burstlike electrical conditioning stimulation (HFS) applied to human skin induces an increase in mechanical pinprick sensitivity of the surrounding unconditioned skin (a phenomenon known as secondary hyperalgesia). The present study assessed the effect of frequency of conditioning stimulation on the development of this increased pinprick sensitivity in humans. In a first experiment, we compared the increase in pinprick sensitivity induced by HFS, using monophasic non-charge-compensated pulses and biphasic charge-compensated pulses. High-frequency stimulation, traditionally delivered with non-charge-compensated square-wave pulses, may induce a cumulative depolarization of primary afferents and/or changes in pH at the electrode-tissue interface due to the accumulation of a net residue charge after each pulse. Both could contribute to the development of the increased pinprick sensitivity in a frequency-dependent fashion. We found no significant difference in the increase in pinprick sensitivity between HFS delivered with charge-compensated and non-charge-compensated pulses, indicating that the possible contribution of charge accumulation when non-charge-compensated pulses are used is negligible. In a second experiment, we assessed the effect of different frequencies of conditioning stimulation (5, 20, 42, and 100 Hz) using charge-compensated pulses on the development of increased pinprick sensitivity. The maximal increase in pinprick sensitivity was observed at intermediate frequencies of stimulation (20 and 42 Hz). It is hypothesized that the stronger increase in pinprick sensitivity at intermediate frequencies may be related to the stronger release of substance P and/or neurokinin-1 receptor activation expressed at lamina I neurons after C-fiber stimulation. NEW & NOTEWORTHY Burstlike electrical conditioning stimulation applied to human skin induces an increase in pinprick sensitivity in the surrounding unconditioned skin (a phenomenon referred to as secondary hyperalgesia). Here we show that the development of the increase in pinprick sensitivity is dependent on the frequency of the burstlike electrical conditioning stimulation.

Within‐ and between‐session reliability of secondary hyperalgesia induced by electrical high‐frequency stimulation

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

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

2022 ◽  
Author(s):  
Rosa Hugosdottir ◽  
Mindy Kasting ◽  
Carsten Dahl Mørch ◽  
Ole Kæseler Andersen ◽  
Lars Arendt-Nielsen
Keyword(s):  
High Frequency ◽  
Blood Perfusion ◽  
Control Area ◽  
High Frequency Stimulation ◽  
Secondary Hyperalgesia ◽  
Capsaicin Application ◽  
Heat Pain Threshold ◽  
Frequency Stimulation ◽  
Topical Capsaicin ◽  
Chronic Pain Conditions

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.

N-Methyl-D-Aspartate Receptor Activation Interacts with Electrical High Frequency Stimulation in the Rat Caudate Nucleus in vitro and in vivo

2014 ◽  
Vol 4 ◽  
pp. 1 ◽  
Author(s):  
Ramya Varatharajan ◽  
Kevin Joseph ◽  
Susanne Loeffler ◽  
Henriette Fuellgraf ◽  
Ulrich G. Hofmann ◽  
...  
Keyword(s):  
Caudate Nucleus ◽  
High Frequency ◽  
Receptor Activation ◽  
High Frequency Stimulation ◽  
Aspartate Receptor ◽  
Frequency Stimulation

Electric Low-Frequency Stimulation of the Tongue Induces Long-Term Depression of the Jaw-Opening Reflex in Anesthetized Mice

2004 ◽  
Vol 92 (6) ◽  
pp. 3332-3337 ◽  
Author(s):  
Jens Ellrich
Keyword(s):  
High Frequency ◽  
Low Frequency ◽  
High Frequency Stimulation ◽  
Conditioning Stimulation ◽  
Low Frequency Stimulation ◽  
Jaw Opening ◽  
Jaw Opening Reflex ◽  
Frequency Stimulation ◽  
Stimulation Of

Long-term depression (LTD) of somatosensory processing has been demonstrated in slice preparations of the spinal dorsal horn. Although LTD could be reliably induced in vitro, inconsistent results were encountered when the same types of experiments were conducted in adult animals in vivo. We addressed the hypothesis that LTD of orofacial sensorimotor processing can be induced in mice under general anesthesia. The effects of electric low- and high-frequency conditioning stimulation of the tongue on the sensorimotor jaw-opening reflex (JOR) elicited by electric tongue stimulation were investigated. Low-frequency stimulation induced a sustained decrease of the reflex integral for ≥1 h after the end of conditioning stimulation. After additional high-frequency stimulation, the reflex partly recovered from LTD. High-frequency stimulation alone induced a transient increase of the JOR integral for <10 min. The LTD of the sensorimotor jaw-opening reflex in anesthetized mice may be an appropriate model to investigate the central mechanisms and the pharmacology of synaptic plasticity in the orofacial region. The application of electrophysiological techniques in mice provides the opportunity to include adequate knock-out models to elucidate the neurobiology of LTD.

Kindling Induces Transient NMDA Receptor–Mediated Facilitation of High-Frequency Input in the Rat Dentate Gyrus

2001 ◽  
Vol 85 (5) ◽  
pp. 2195-2202 ◽  
Author(s):  
Joachim Behr ◽  
Uwe Heinemann ◽  
Istvan Mody
Keyword(s):  
Nmda Receptor ◽  
Dentate Gyrus ◽  
High Frequency ◽  
Time Course ◽  
Critical Role ◽  
Receptor Activation ◽  
Kainate Receptors ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Gating Mechanism

To elucidate the gating mechanism of the epileptic dentate gyrus on seizure-like input, we investigated dentate gyrus field potentials and granule cell excitatory postsynaptic potentials (EPSPs) following high-frequency stimulation (10–100 Hz) of the lateral perforant path in an experimental model of temporal lobe epilepsy (i.e., kindled rats). Although control slices showed steady EPSP depression at frequencies greater than 20 Hz, slices taken from animals 48 h after the last seizure presented pronounced EPSP facilitation at 50 and 100 Hz, followed by steady depression. However, 28 days after kindling, the EPSP facilitation was no longer detectable. Using the specific N-methyl-d-aspartate (NMDA) and RS-α-amino-3-hydroxy-5-methyl-4-isoxazoleproponic acid (AMPA) receptor antagonists 2-amino-5-phosphonovaleric acid and SYM 2206, we examined the time course of alterations in glutamate receptor–dependent synaptic currents that parallel transient EPSP facilitation. Forty-eight hours after kindling, the fractional AMPA and NMDA receptor–mediated excitatory postsynaptic current (EPSC) components shifted dramatically in favor of the NMDA receptor–mediated response. Four weeks after kindling, however, AMPA and NMDA receptor–mediated EPSCs reverted to control-like values. Although the granule cells of the dentate gyrus contain mRNA-encoding kainate receptors, neither single nor repetitive perforant path stimuli evoked kainate receptor–mediated EPSCs in control or in kindled rats. The enhanced excitability of the kindled dentate gyrus 48 h after the last seizure, as well as the breakdown of its gating function, appear to result from transiently enhanced NMDA receptor activation that provides significantly slower EPSC kinetics than those observed in control slices and in slices from kindled animals with a 28-day seizure-free interval. Therefore, NMDA receptors seem to play a critical role in the acute throughput of seizure activity and in the induction of the kindled state but not in the persistence of enhanced seizure susceptibility.

The effect of high-frequency conditioning stimulation of human skin on reported pain intensity and event-related potentials

2012 ◽  
Vol 108 (8) ◽  
pp. 2276-2281 ◽  
Author(s):  
Emanuel N. van den Broeke ◽  
Casper H. van Heck ◽  
Linda A. J. M. Ceelen ◽  
Clementina M. van Rijn ◽  
Harry van Goor ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Human Skin ◽  
High Frequency ◽  
Pain Sensitivity ◽  
Event Related Potentials ◽  
Conditioning Stimulation ◽  
Skin Site ◽  
Electrical Test ◽  
Related Potentials ◽  
Electrical Stimuli

High-frequency conditioning electrical stimulation (HFS) of human skin induces an increased pain sensitivity to mechanical stimuli in the surrounding nonconditioned skin. The aim of this study was to investigate the effect of HFS on reported pain sensitivity to single electrical stimuli applied within the area of conditioning stimulation. We also investigated the central nervous system responsiveness to these electrical stimuli by measuring event-related potentials (ERPs). Single electrical test stimuli were applied in the conditioned area before and 30 min after HFS. During electrical test stimulation, the reported pain intensity (numerical rating scale) and EEG (ERPs) were measured. Thirty minutes after conditioning stimulation, we observed a decrease of reported pain intensity at both the conditioned and control (opposite arm) skin site in response to the single electrical test stimuli. In contrast, we observed enhanced ERP amplitudes after HFS at the conditioned skin site, compared with control site, in response to the single electrical test stimuli. Recently, it has been proposed that ERPs, at least partly, reflect a saliency detection system. Therefore, the enhanced ERPs might reflect enhanced saliency to potentially threatening stimuli.

scholarly journals Cholinergic mechanisms of high-frequency stimulation in entopeduncular nucleus

2016 ◽  
Vol 115 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Feng Luo ◽  
Zelma H. T. Kiss
Keyword(s):  
High Frequency ◽  
Receptor Activation ◽  
Inhibitory Synapses ◽  
High Frequency Stimulation ◽  
Entopeduncular Nucleus ◽  
Cellular Mechanisms ◽  
Cholinergic Mechanism ◽  
Whole Cell Patch Clamp ◽  
Frequency Stimulation ◽  
Underlying Mechanisms

Chronic, high-frequency (>100 Hz) electrical stimulation, known as deep brain stimulation (DBS), of the internal segment of the globus pallidus (GPi) is a highly effective therapy for Parkinson's disease (PD) and dystonia. Despite some understanding of how it works acutely in PD models, there remain questions about its mechanisms of action. Several hypotheses have been proposed, such as depolarization blockade, activation of inhibitory synapses, depletion of neurotransmitters, and/or disruption/alteration of network oscillations. In this study we investigated the cellular mechanisms of high-frequency stimulation (HFS) in entopeduncular nucleus (EP; rat equivalent of GPi) neurons using whole cell patch-clamp recordings. We found that HFS applied inside the EP nucleus induced a prolonged afterdepolarization that was dependent on stimulation frequency, pulse duration, and current amplitude. The high frequencies (>100 Hz) and pulse widths (>0.15 ms) used clinically for dystonia DBS could reliably induce these afterdepolarizations, which persisted under blockade of ionotropic glutamate (kynurenic acid, 2 mM), GABAA (picrotoxin, 50 μM), GABAB (CGP 55845, 1 μM), and acetylcholine nicotinic receptors (DHβE, 2 μM). However, this effect was blocked by atropine (2 μM; nonselective muscarinic antagonist) or tetrodotoxin (0.5 μM). Finally, the muscarinic-dependent afterdepolarizations were sensitive to Ca2+-sensitive nonspecific cationic (CAN) channel blockade. Hence, these data suggest that muscarinic receptor activation during HFS can lead to feedforward excitation through the opening of CAN channels. This study for the first time describes a cholinergic mechanism of HFS in EP neurons and provides new insight into the underlying mechanisms of DBS.

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