nociceptive system
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Pain ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Lou Cathenaut ◽  
Benjamin Leonardon ◽  
Robin Kuster ◽  
Perrine Inquimbert ◽  
Rémy Schlichter ◽  
...  

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
André Mouraux ◽  
Petra Bloms-Funke ◽  
Irmgard Boesl ◽  
Ombretta Caspani ◽  
Sonya C. Chapman ◽  
...  

Abstract Background IMI2-PainCare-BioPain-RCT3 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics, by providing a quantitative understanding between drug exposure and effects of the drug on nociceptive signal processing in human volunteers. IMI2-PainCare-BioPain-RCT3 will focus on biomarkers derived from non-invasive electroencephalographic (EEG) measures of brain activity. Methods This is a multisite single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects. Biomarkers derived from scalp EEG measurements (laser-evoked brain potentials [LEPs], pinprick-evoked brain potentials [PEPs], resting EEG) will be obtained before and three times after administration of three medications known to act on the nociceptive system (lacosamide, pregabalin, tapentadol) and placebo, given as a single oral dose in separate study periods. Medication effects will be assessed concurrently in a non-sensitized normal condition and a clinically relevant hyperalgesic condition (high-frequency electrical stimulation of the skin). Patient-reported outcomes will also be collected. A sequentially rejective multiple testing approach will be used with overall alpha error of the primary analysis split between LEP and PEP under tapentadol. Remaining treatment arm effects on LEP or PEP or effects on EEG are key secondary confirmatory analyses. Complex statistical analyses and PK-PD modeling are exploratory. Discussion LEPs and PEPs are brain responses related to the selective activation of thermonociceptors and mechanonociceptors. Their amplitudes are dependent on the responsiveness of these nociceptors and the state of the pathways relaying nociceptive input at the level of the spinal cord and brain. The magnitude of resting EEG oscillations is sensitive to changes in brain network function, and some modulations of oscillation magnitude can relate to perceived pain intensity, variations in vigilance, and attentional states. These oscillations can also be affected by analgesic drugs acting on the central nervous system. For these reasons, IMI2-PainCare-BioPain-RCT3 hypothesizes that EEG-derived measures can serve as biomarkers of target engagement of analgesic drugs for future Phase 1 clinical trials. Phase 2 and 3 clinical trials could also benefit from these tools for patient stratification. Trial registration This trial was registered 25/06/2019 in EudraCT (2019%2D%2D001204-37).


2021 ◽  
Vol 34 (2) ◽  
pp. 139-153
Author(s):  
Boudewijn van den Berg ◽  
Jan R. Buitenweg

AbstractMonitoring nociceptive processing is a current challenge due to a lack of objective measures. Recently, we developed a method for simultaneous tracking of psychophysical detection probability and brain evoked potentials in response to intra-epidermal stimulation. An exploratory investigation showed that we could quantify nociceptive system behavior by estimating the effect of stimulus properties on the evoked potential (EP). The goal in this work was to accurately measure nociceptive system behavior using this method in a large group of healthy subjects to identify the locations and latencies of EP components and the effect of single- and double-pulse stimuli with an inter-pulse interval of 10 or 40 ms on these EP components and detection probability. First, we observed the effect of filter settings and channel selection on the EP. Subsequently, we compared statistical models to assess correlation of EP and detection probability with stimulus properties, and quantified the effect of stimulus properties on both outcome measures through linear mixed regression. We observed lateral and central EP components in response to intra-epidermal stimulation. Detection probability and central EP components were positively correlated to the amplitude of each pulse, regardless of the inter-pulse interval, and negatively correlated to the trial number. Both central and lateral EP components also showed strong correlation with detection. These results show that both the observed EP and the detection probability reflect the various steps of processing of a nociceptive stimulus, including peripheral nerve fiber recruitment, central synaptic summation, and habituation to a repeated stimulus.


2021 ◽  
Author(s):  
A. Hurth

Previous studies investigating spatial acuity measured by two-point discrimination threshold concluded that the nociceptive system is less accurate than the innocuous tactile system. In the discussed article, the authors point out that the nociceptive system is more accurate than the tactile system when controlling for the stimulus modality and intensity in healthy pain-free individuals. Furthermore, this article shows that the pattern of distance-based and areabased spatial summation of pain is modality independent.


2020 ◽  
Vol 80 (4) ◽  
pp. 267-275
Author(s):  
Taís Campos Lima ◽  
Júlia Borges Paes Lemes ◽  
Tauane Franco Pinheiro Alves Capop ◽  
Lorena Borges Lima ◽  
Celina Lotufo

2020 ◽  
Vol 24 (5) ◽  
pp. 956-966
Author(s):  
Giulia Di Stefano ◽  
Andrea Di Lionardo ◽  
Silvia La Cesa ◽  
Giuseppe Di Pietro ◽  
Alessandra Fasolino ◽  
...  

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