Skin denervation does not alter cortical potentials to surface concentric electrode stimulation: A comparison with laser evoked potentials and contact heat evoked potentials

Cesa, S. La; Stefano, Giulia Di; Leone, C.; Pepe, Alessia; Galosi, Eleonora; Alù, Francesca; Fasolino, Alessandra; Cruccu, G.; Valeriani, Massimiliano; Truini, Andrea

doi:10.1002/ejp.1112

Cited by 38 publications

(27 citation statements)

References 29 publications

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“…As predicted based on LEP studies in humans 35,36 , peripheral application of capsaicin (causing defunctionalisation of C-fibres 30 ) resulted in a large reduction in the amplitude of the LEP. This was accompanied by a significant reduction in the number of withdrawal responses to a given intensity of laser stimulation.…”

Section: Discussionmentioning

confidence: 64%

Trial by trial, machine learning approach identifies temporally discrete Aδ- and C-fibre mediated laser evoked potentials that predict pain behaviour in rats

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Blockeel

Huxter³

et al. 2021

Preprint

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Laser evoked potentials (LEPs) – the EEG response to temporally-discrete thermal stimuli – are commonly used in experimental pain studies in humans. Such stimuli selectively activate nociceptors and produce EEG features which correlate with pain intensity. The rodent LEP has been proposed to be a translational biomarker of nociception and pain, however its validity has been questioned because of reported differences in the classes of nociceptive fibres mediating the response. Here we use a machine learning, trial by trial analysis approach on wavelet-denoised LEPs generated by stimulation of the plantar hindpaw of rats. The LEP amplitude was more strongly related to behavioural response than to laser stimulus energy. A simple decision tree classifier using LEP features was able to predict behavioural responses with 73% accuracy. An examination of the features used by the classifier showed that mutually exclusive short and long latency LEP peaks were clearly seen in single-trial data, yet were not evident in grand average data pooled from multiple trials. This bimodal distribution of LEP latencies was mirrored in the paw withdrawal latencies which were preceded and predicted by the LEP responses. The proportion of short latency events was increased after intradermal application of high dose capsaicin (to defunctionalise TRPV1 expressing nociceptors), suggesting they were mediated by Aδ-fibres (specifically AMH-I). These findings demonstrate that both C- and Aδ-fibres contribute to rodent LEPs and concomitant behavioural responses, providing a real-time assay of specific fibre function in conscious animals. Single-trial analysis approaches can improve the utility of LEPs as a translatable biomarker of pain.

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Section: Discussionmentioning

confidence: 64%

Trial by trial, machine learning approach identifies temporally discrete Aδ- and C-fibre mediated laser evoked potentials that predict pain behaviour in rats

Sales

Blockeel

Huxter³

et al. 2021

Preprint

Self Cite

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“…Notably, the specificity for nociceptive fibers of PCES is still controversially debated [ 34 , 35 ]. The aim of the present study was to further elucidate the understanding of this recently introduced CPM model using PCES as TS with additionally recording of PCES evoked cortical potentials [ 20 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Painful Cutaneous Electrical Stimulation vs. Heat Pain as Test Stimuli in Conditioned Pain Modulation

et al. 2020

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Different paradigms can assess the effect of conditioned pain modulation (CPM). The aim of the present study was to compare heat pain, as an often used test stimulus (TS), to painful cutaneous electrical stimulation (PCES), having the advantage of the additional recording of PCES-related evoked potentials. In 28 healthy subjects we applied heat and PCES at the dominant hand as test stimulus (TS) to compare the CPM-effect elicited by hand immersion into cold water (10 °C) as conditioning stimulus (CS). Subjects rated the pain intensity of TS at baseline, during and 5 min after CS application and additionally of CS, on a numerical rating scale (NRS) (0–100). The ‘early’ (during CS–before CS) and ‘late’ (after CS–before CS) CPM-effects were analyzed. Parallel to the PCES, the related evoked potentials were recorded via Cz to evaluate any changes in PCES-amplitudes. CS reduced significantly the pain intensity of both PCES and heat pain as TS. On a group level, the CPM-effect did not differ significantly between both paradigms. Both early and late CPM-effect based on PCES correlated significantly with the CS pain intensity (r = −0.630 and −0.503, respectively), whereas using heat pain the correlation was not significant. We found a significant reduction of PCES-amplitudes during CS, but this did not correlate with the PCES-induced pain intensity. Correlation with the CS painfulness (r = −0.464) did not achieve the significance level after Bonferroni correction. The extent of the CPM effects was similar in both testing paradigms at group level, despite intraindividual differences. Future studies should further elicit the exact mechanisms explaining the modality of these specific differences.

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“…The two most commonly employed methods are those of contact heat evoked potentials (CHEP'S) and laser evoked potentials (LEP's). A recent study has demonstrated excellent sensitivity and specificity for laser evoked potentials with abnormal pinprick sensitivity and reduced IENFD in diabetic neuropathy …”

Section: Small Fibre Functionmentioning

confidence: 99%

“…A recent study has demonstrated excellent sensitivity and specificity for laser evoked potentials with abnormal pinprick sensitivity and reduced IENFD in diabetic neuropathy. 23…”

Section: Evoked Potentialsmentioning

confidence: 99%

Diabetic neuropathy: A focus on small fibres

Malik

2019

Diabetes Metabolism Res

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Diabetic peripheral neuropathy (DPN) is diagnosed too late, which contrasts with our approach for diabetic retinopathy and nephropathy, where incipient disease is detected early enabling timely treatment. The 10‐g monofilament and a foot exam are the commonly used methods for screening diabetic neuropathy, but this primarily identifies moderate to severe diabetic neuropathy. Small fibres are damaged early and are associated with the development of painful diabetic neuropathy, foot ulceration, and Charcot foot. Tests of small fibre damage include thermal thresholds, microneurography, evoked potentials, sudomotor function, laser Doppler flare, skin biopsy, and corneal confocal microscopy. Measures of small fibre damage and repair may be key to the assessment of efficacy in clinical trials of disease modifying therapies for diabetic neuropathy.

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Skin denervation does not alter cortical potentials to surface concentric electrode stimulation: A comparison with laser evoked potentials and contact heat evoked potentials

Cited by 38 publications

References 29 publications

Trial by trial, machine learning approach identifies temporally discrete Aδ- and C-fibre mediated laser evoked potentials that predict pain behaviour in rats

Trial by trial, machine learning approach identifies temporally discrete Aδ- and C-fibre mediated laser evoked potentials that predict pain behaviour in rats

Painful Cutaneous Electrical Stimulation vs. Heat Pain as Test Stimuli in Conditioned Pain Modulation

Diabetic neuropathy: A focus on small fibres

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