Contact Heat Evoked Potential Stimulator Research Articles

Objective assessment of mental nerve local anesthesia

To study the reaction of the mental nerve to selective stimulation of thin nerve fibers by thermal stimuli during conduction anesthesia. The pilot study involved 24 healthy volunteers: 13 subjects were injected with a 4% solution of articaine-containing anesthetic with a vasoconstrictor in a ratio of 1:200 000 (pH 4.8-5.4) and 11 subjects - a 3% solution of mepivacaine-containing local anesthetic without a vasoconstrictor (pH value 5.8-6.4). The registration of evoked potentials was performed twice: before local anesthesia and 5 minutes after anesthesia. With the help of disposable carpal dental injectors, local anesthesia was performed near the mental foramen in order to anesthetize the innervation region of the mental nerve through a conductive type. The evoked potentials (VP) were recorded on a Nicolet instrument (USA) with Bravo evoked potentials software. The study of thermal EPs was performed using a Contact heat evoked potential stimulator (CHEPS) device ('Medoc Ltd, Ramat Yishai', Israel). The base and peak temperature were set at 33 and 54 °C, correspondingly. The evoked potentials for thermal stimulation demonstrated a significant decrease in the amplitude of all components and the elongation of the LP of the main negative-positive N2-P2 complex after anesthesia compared with the initial thermal EP. The complete disappearance of thermal responses was observed in 14 (58%) of 24 study participants, minor changes were seen in 3 (12.5%) cases only. The total response disappearance was observed in 10 (77%) of 13 participants after articaine and in 3 (27%) of 11 - after mepivacaine (p<0.05), weak changes were registered in 2 (15%) cases in the articaine group and in 1 (9%) case in the mepivacaine group. A 4% solution of articaine is somewhat more effective for pain relief of teeth and bone since it often causes deeper anesthesia, and a 3% solution of mepivacaine without a vasoconstrictor is physiologically more suitable for working with soft tissues.

Measurements of Temporal Summation of Heat Pain: a Pilot Investigation in Healthy Humans

Temporal summation of pain (TSP) is a promising tool for measuring the pain modulation processes in healthy subjects and patients with chronic pain. We tried to find optimal stimulation parameters in order to elicit a robust reproducible TSP phenomenon. Twenty healthy volunteers (15 women and 5 men) completed four sessions/conditions of pulsating heat pain stimulation, applied to the left forearm with a frequency of 0.33–0.4 sec–1 using a contact heat-evoked potential stimulator. The stimulation temperature (step +0.5°C or +1.0°C up to the pain threshold, pain tolerance), pulse duration (500, 800, or 1000 msec), and number of stimuli (60 or 90) were varied. The participants rated the pain intensity at the first and every 10th heat pulse, using a numeric rating scale (NRS) 0–100. The TSP was calculated as the difference between the lowest rating and the rating of the last stimulus and was compared between conditions. The optimal condition (19 out of 20 participants responded with TSP) showed temperature at pain tolerance, pulse duration of 800 msec, and 90 stimuli. In addition, this condition showed weaker side effects (painful discomfort) than those with less (60) but longer (1000 msec) stimuli presented 1.0 degree above the pain threshold. The protocol with a relatively high stimulus repetition and a moderate pulse duration seems to be the optimal protocol to reproduce TSP. Heat stimulation with longer pulse durations and higher stimulation temperatures was less feasible.

Migraine Does Not Affect Pain Intensity Perception: A Cross-Sectional Study.

To explore perceived pain intensity (PPI) in three drug-naïve patient groups characterized by homogeneous migraine phenotypes-migraine without aura without cutaneous allodynia (MwoA CA-), MwoA with ictal CA (MwoA CA+), and migraine with aura without cutaneous allodynia (MwA CA-)-compared with age- and sex-matched healthy controls (HCs). Using trigeminal heat stimulation (THS) at three different predefined intensities (41 °C, 51 °C, and 53 °C) performed by the contact heat-evoked potential stimulator (CHEPS), PPI was investigated in 34 patients with MwoA CA-, 30 patients with MwoA CA+, and 30 patients with MwA CA- compared with 30 age- and sex-matched HCs. The patients had never taken migraine-preventive drugs, and they were investigated during an interictal period to avoid confounds associated with migraine attack. Secondary analyses evaluated associations between PPI and clinical features of migraine in patients. No significant differences were observed between the four groups for each experimentally induced stimulus. Moreover, no significant correlations were found between clinical variables and the PPI of the THS at any level of experimental stimulus. Despite the converging evidence of pain threshold abnormalities in migraine patients, our findings suggest that migraine patients did not exhibit differences in the PPI of THS when compared with HCs, independent of phenotype and migraine severity, as well as somatic, psychiatric, or pharmacological interferences. This may depend on both the nature of the pain stimulus experienced and the involvement of selective regions or specific pain processing pathways.

Preliminary findings of cerebral responses on transcutaneous vagal nerve stimulation on experimental heat pain.

Transcutaneous vagal nerve stimulation (TVNS) is a promising complementary method of pain relief. However, the neural networks associated with its analgesic effects are still to be elucidated. Therefore, we conducted two functional magnetic resonance imaging (fMRI) sessions, in a randomized order, with twenty healthy subjects who were exposed to experimental heat pain stimulation applied to the right forearm using a Contact Heat-Evoked Potential Stimulator. While in one session TVNS was administered bilaterally to the concha auriculae with maximal, non-painful intensity, the stimulation device was switched off in the other session (placebo condition). Pain thresholds were measured before and after each session. Heat stimulation elicited fMRI activation in cerebral pain processing regions. Activation magnitude in the secondary somatosensory cortex, posterior insula, anterior cingulate and caudate nucleus was associated with heat stimulation without TVNS. During TVNS, this association was only seen for the right anterior insula. TVNS decreased fMRI signals in the anterior cingulate cortex in comparison with the placebo condition; however, there was no relevant pain reducing effect over the group as a whole. In contrast, TVNS compared to the placebo condition showed an increased activation in the primary motor cortex, contralateral to the site of heat stimulation, and in the right amygdala. In conclusion, in the protocol used here, TVNS specifically modulated the cerebral response to heat pain, without having a direct effect on pain thresholds.

P017. Ictal cutaneous allodynia does not affect pain perception in patients with migraine: a trigeminal heat stimulation study during interictal period.

Background Migraine is a disabling neurological condition characterized by headache attacks, hypersensitivities to visual, auditory, olfactory and somatosensory stimuli, nausea and vomiting. Peripheral and central sensitization of trigeminovascular neurons seem to play a critical role in different aspects of migraine pathophysiology [1]. In the last years, several studies investigated pain thresholds in patients with migraine during both attacks and interictal periods. However, pain perception in patients with migraine has been poorly explored. Objective To investigate perception intensity of trigeminal heat stimulation (THS) [2] in patients with migraine without (MwoA CA-) and with allodynia (MwoA CA+) compared to healthy controls (HC) and correlation with clinical parameters of migraine severity. Methods We enrolled 80 patients with migraine (40 patients with MwoA CA- and 40 patients with MwoA CA+) and 60 HC. THS was performed using the contact heat evoked potential stimulator (CHEPS) at three different intensities: a low-innocuous stimulus at 41°C and two painful heat stimuli at 51° and 53°C (to provide a moderate-noxious and a high-noxious stimulus). Subjects had to verbally rate the intensity perception of the experimental stimulus by means of a numerical rating scale (NRS) ranging from 0( “no pain” )t o 10 (“worst pain imaginable”). Results NRS of pain perception was not significantly different between patients with MwoA (as a group) and HC at any level of experimental stimuli. The absence of significant differences in pain perception was also found between patient groups defined as patients with MwoA CA- and with MwoA CA+ compared to HC, at any level of experimental stimuli. Conclusions

The Effect of Oral Morphine on Pain-Related Brain Activation - An Experimental Functional Magnetic Resonance Imaging Study.

Knowledge about cerebral mechanisms underlying pain perception and effect of analgesic drugs is important for developing methods for diagnosis and treatment of pain. The aim was to explore altered brain activation before and after morphine treatment using functional magnetic resonance imaging recorded during experimental painful heat stimulation. Functional magnetic resonance imaging data were recorded and analysed in 20 healthy volunteers (13 men and 7 women, 24.9 ± 2.6 years) in a randomized, double-blind, placebo-controlled, cross-over study. Painful stimulations were applied to the right forearm using a contact heat evoked potential stimulator (CHEPS) before and after treatment with 30 mg oral morphine and placebo. CHEPS stimulations before treatment induced activation in the anterior cingulate cortex, secondary somatosensory cortex/insula, thalamus and cerebellum (n = 16, p < 0.05). In response to morphine treatment, the spatial extent of these pain-specific areas decreased (n = 20). Reduced pain-induced activation was seen in the right insula, anterior cingulate cortex and inferior parietal cortex after morphine treatment compared to before treatment (n = 16, p < 0.05), and sensory ratings of pain perception were significantly reduced after morphine treatment (p = 0.02). No effect on pain-induced brain activation was seen after placebo treatment compared to before treatment (n = 12, p > 0.05). In conclusion, heat stimulation activated areas in the 'pain matrix' and a clinically relevant dose of orally administered morphine revealed significant changes in brain areas where opioidergic pathways are predominant. The method may be useful to investigate the mechanisms of analgesics.

The use of contact heat evoked potential stimulator (CHEPS) in magnetoencephalography for pain research

BackgroundContact heat evoked potentials (CHEP) is a thermal stimulus modality used in pain research. We examine a commercial CHEP stimulator (CHEPS) that is designed to work in an fMRI environment, but poorly understood in the MEG environment. The CHEPS attains target temperatures rapidly using sophisticated control signals that unfortunately induce artifacts in the MEG. In this paper, we summarize our experiences using the CHEPS in MEG to study pain using an experimental paradigm, and propose a novel method for managing its artifact. New methodWe introduce a novel damped sinusoid modeling (DSM) technique to remove the CHEPS artifact based on estimates of the underlying sinusoids and damping factors. We show comparisons to signal space projection (SSP) and temporal signal space separation (tSSS) methods. ResultsThe CHEPS artifact is highly dynamic, yet deterministic, switching rapidly from one frequency to another, with different spatial components. The galvanic connection between the subject and the CHEPS probe alters its performance, making pre-characterization difficult. Comparison with existing methodsSSP methods failed to remove the artifact completely. TSSS performed better than SSP; however, tSSS requires the use of a multipolar head model that decreases the dimensionality and possibly the information content of the data. In contrast, DSM offers a strictly temporal modeling approach in which the artifact is estimated as a sum of damped sinusoids which is subtracted from the data. ConclusionThough the CHEPS increases the noise floor and introduces artifacts to the data, we believe the device can be successfully used in MEG if appropriate artifact removal techniques are followed.

Functional MRI brain imaging studies using the Contact Heat Evoked Potential Stimulator (CHEPS) in a human volunteer topical capsaicin pain model

Acute application of topical capsaicin produces spontaneous burning and stinging pain similar to that seen in some neuropathic states, with local hyperalgesia. Use of capsaicin applied topically or injected intradermally has been described as a model for neuropathic pain, with patterns of activation in brain regions assessed using functional magnetic resonance imaging (fMRI) and positron emission tomography. The Contact Heat Evoked Potential Stimulator (CHEPS) is a noninvasive clinically practical method of stimulating cutaneous A-delta nociceptors. In this study, topical capsaicin (1%) was applied to the left volar forearm for 15 minutes of twelve adult healthy human volunteers. fMRI scans and a visual analog pain score were recorded during CHEPS stimulation precapsaicin and postcapsaicin application. Following capsaicin application there was a significant increase in visual analog scale (mean ± standard error of the mean; precapsaicin 26.4 ± 5.3; postcapsaicin 48.9 ± 6.0; P < 0.0001). fMRI demonstrated an overall increase in areas of activation, with a significant increase in the contralateral insular signal (mean ± standard error of the mean; precapsaicin 0.434 ± 0.03; postcapsaicin 0.561 ± 0.07; P = 0.047). The authors of this paper recently published a study in which CHEPS-evoked A-delta cerebral potential amplitudes were found to be decreased postcapsaicin application. In patients with neuropathic pain, evoked pain and fMRI brain responses are typically increased, while A-delta evoked potential amplitudes are decreased. The protocol of recording fMRI following CHEPS stimulation after topical application of capsaicin could be combined with recording of evoked potentials to provide a simple, rapid, and robust volunteer model to develop novel drugs for neuropathic pain.

Effective electromagnetic noise cancellation with beamformers and synthetic gradiometry in shielded and partly shielded environments

The major challenge of MEG, the inverse problem, is to estimate the very weak primary neuronal currents from the measurements of extracranial magnetic fields. The non-uniqueness of this inverse solution is compounded by the fact that MEG signals contain large environmental and physiological noise that further complicates the problem. In this paper, we evaluate the effectiveness of magnetic noise cancellation by synthetic gradiometers and the beamformer analysis method of synthetic aperture magnetometry (SAM) for source localisation in the presence of large stimulus-generated noise. We demonstrate that activation of primary somatosensory cortex can be accurately identified using SAM despite the presence of significant stimulus-related magnetic interference. This interference was generated by a contact heat evoked potential stimulator (CHEPS), recently developed for thermal pain research, but which to date has not been used in a MEG environment. We also show that in a reduced shielding environment the use of higher order synthetic gradiometry is sufficient to obtain signal-to-noise ratios (SNRs) that allow for accurate localisation of cortical sensory function.

Contact heat evoked potentials using simultaneous EEG and fMRI and their correlation with evoked pain

BackgroundThe Contact Heat Evoked Potential Stimulator (CHEPS) utilises rapidly delivered heat pulses with adjustable peak temperatures to stimulate the differential warm/heat thresholds of receptors expressed by Aδ and C fibres. The resulting evoked potentials can be recorded and measured, providing a useful clinical tool for the study of thermal and nociceptive pathways. Concurrent recording of contact heat evoked potentials using electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) has not previously been reported with CHEPS. Developing simultaneous EEG and fMRI with CHEPS is highly desirable, as it provides an opportunity to exploit the high temporal resolution of EEG and the high spatial resolution of fMRI to study the reaction of the human brain to thermal and nociceptive stimuli.MethodsIn this study we have recorded evoked potentials stimulated by 51°C contact heat pulses from CHEPS using EEG, under normal conditions (baseline), and during continuous and simultaneous acquisition of fMRI images in ten healthy volunteers, during two sessions. The pain evoked by CHEPS was recorded on a Visual Analogue Scale (VAS).ResultsAnalysis of EEG data revealed that the latencies and amplitudes of evoked potentials recorded during continuous fMRI did not differ significantly from baseline recordings. fMRI results were consistent with previous thermal pain studies, and showed Blood Oxygen Level Dependent (BOLD) changes in the insula, post-central gyrus, supplementary motor area (SMA), middle cingulate cortex and pre-central gyrus. There was a significant positive correlation between the evoked potential amplitude (EEG) and the psychophysical perception of pain on the VAS.ConclusionThe results of this study demonstrate the feasibility of recording contact heat evoked potentials with EEG during continuous and simultaneous fMRI. The combined use of the two methods can lead to identification of distinct patterns of brain activity indicative of pain and pro-nociceptive sensitisation in healthy subjects and chronic pain patients. Further studies are required for the technique to progress as a useful tool in clinical trials of novel analgesics.

Use of the novel Contact Heat Evoked Potential Stimulator (CHEPS) for the assessment of small fibre neuropathy: correlations with skin flare responses and intra-epidermal nerve fibre counts.

BackgroundThe Contact Heat Evoked Potential Stimulator (CHEPS) rapidly stimulates cutaneous small nerve fibres, and resulting evoked potentials can be recorded from the scalp. We have studied patients with symptoms of sensory neuropathy and controls using CHEPS, and validated the findings using other objective measures of small nerve fibres i.e. the histamine-induced skin flare response and intra-epidermal fibres (IEF), and also quantitative sensory testing (QST), a subjective measure.MethodsIn patients with symptoms of sensory neuropathy (n = 41) and healthy controls (n = 9) we performed clinical examination, QST (monofilament, vibration and thermal perception thresholds), nerve conduction studies, histamine-induced skin flares and CHEPS. Skin punch biopsies were immunostained using standard ABC immunoperoxidase for the nerve marker PGP 9.5 or the heat and capsaicin receptor TRPV1. Immunoreactive IEF were counted per length of tissue section and epidermal thickness recorded.ResultsAmplitudes of Aδ evoked potentials (μV) following face, arm or leg stimulation were reduced in patients (e.g. for the leg: mean ± SEM – controls 11.7 ± 1.95, patients 3.63 ± 0.85, p = 0.0032). Patients showed reduced leg skin flare responses, which correlated with Aδ amplitudes (rs = 0.40, p = 0.010). In patient leg skin biopsies, PGP 9.5- and TRPV1-immunoreactive IEF were reduced and correlated with Aδ amplitudes (PGP 9.5, rs = 0.51, p = 0.0006; TRPV1, rs = 0.48, p = 0.0012).ConclusionCHEPS appears a sensitive measure, with abnormalities observed in some symptomatic patients who did not have significant IEF loss and/or QST abnormalities. Some of the latter patients may have early small fibre dysfunction or ion channelopathy. CHEPS provides a clinically practical, non-invasive and objective measure, and can be a useful additional tool for the assessment of sensory small fibre neuropathy. Although further evaluation is required, the technique shows potential clinical utility to differentiate neuropathy from other chronic pain states, and provide a biomarker for analgesic development.

226 A feasibility study of EEG and fMRI co-activation with CHEPS (contact heat evoked potential stimulator)

226 A feasibility study of EEG and fMRI co-activation with CHEPS (contact heat evoked potential stimulator)