The Relationship between Nociceptive Detection Thresholds and Pressure- and Electrical Pain Thresholds: An Explorative Study in Rheumatoid Arthritis Patients.

Recently, methods have been developed enabling the characterization of the nociceptive function at the detection threshold level by measuring nociceptive detection thresholds (NDTs), rather than at the level of the pain threshold via pain threshold (PT) measurements. Both NDT and PT measurements aim to characterize (parts of) the nociceptive system. To date it is unclear if, and if so to what extent, the two outcomes relate to one another. In this study, the primary aim is to explore the relationship between the two measures in patients with rheumatoid arthritis (RA). As secondary aim, we explore differences in NDT between these RA patients with age- and sex-matched healthy controls (HC) from a readily existing dataset. In total 46 RA patients have been recruited, whereby the pressure- (PPT; bilaterally at two locations) and electrical (EPT) pain threshold were evaluated, as well as the NDTs. Significant, positive correlations were found between the EPT and PPT (R=0.54-0.60), but not with the NDTs (R≤0.25). As compared to HC, higher NDTs were found in the RA group. As the presence of a statistically significant weak relationship can only be evaluated using a larger sample size, our results indicate that there is no moderate or stronger relation between PT and NDT outcomes. This implicates that the two outcomes are not strongly driven by the same (nociceptive) mechanism(s). Future research into NDTs and what factors and/or mechanisms affect the outcome, could yield relevant insights into how to use and interpret the results of this relatively new method.Clinical Relevance - The evaluation of nociceptive detection thresholds, in isolation or together with conventionally evaluated pain thresholds, might provide valuable and complementary insights into nociceptive (dis)function in man.

Analysis Of Nociceptive Evoked Potentials During Multi-Stimulus Experiments Using Linear Mixed Models.

Neural processing of sensory stimuli can be studied using EEG by estimation of the evoked potential using the averages of large sets of trials. However, it is not always possible to include all stimulus parameters in a conventional analysis, since this would lead to an insufficient amount of trials to obtain the evoked potential by averaging. Linear mixed models use dependencies within the data to combine information from all data for the estimation of the evoked potential. In this work, it is shown that in multi-stimulus EEG data the quality of an evoked potential estimate can be improved by using a linear mixed model. Furthermore, the linear mixed model effectively deals with correlation between parameters in the data and reveals the influence of individual stimulus parameters.

Electrode alignment of transverse tripoles using a percutaneous triple-lead approach in spinal cord stimulation.

The aim of this modeling study is to determine the influence of electrode alignment of transverse tripoles on the paresthesia coverage of the pain area in spinal cord stimulation, using a percutaneous triple-lead approach. Transverse tripoles, comprising a central cathode and two lateral anodes, were modeled on the low-thoracic vertebral region (T10-T12) using percutaneous triple-lead configurations, with the center lead on the spinal cord midline. The triple leads were oriented both aligned and staggered. In the staggered configuration, the anodes were offset either caudally (caudally staggered) or rostrally (rostrally staggered) with respect to the midline cathode. The transverse tripolar field steering with the aligned and staggered configurations enabled the estimation of dorsal column fiber thresholds (I(DC)) and dorsal root fiber thresholds (I(DR)) at various anodal current ratios. I(DC) and I(DR) were considerably higher for the aligned transverse tripoles as compared to the staggered transverse tripoles. The aligned transverse tripoles facilitated deeper penetration into the medial dorsal columns (DCs). The staggered transverse tripoles always enabled broad and bilateral DC activation, at the expense of mediolateral steerability. The largest DC recruited area was obtained with the rostrally staggered transverse tripole. Transverse tripolar geometries, using percutaneous leads, allow for selective targeting of either medial or lateral DC fibers, if and only if the transverse tripole is aligned. Steering of anodal currents between the lateral leads of the staggered transverse tripoles cannot target medially confined populations of DC fibers in the spinal cord. An aligned transverse tripolar configuration is strongly recommended, because of its ability to provide more post-operative flexibility than other configurations.

Extracellular detection of active membrane currents in the neuron-electrode interface.

Although measurement of sealing resistance is an important tool in the assessment of the electrical contacts between cultured cells and substrate embedded microelectrodes, it does not offer information about the type of cell, i.e. neuron or non-neuronal cell. Also, rules for translation of a measured sealing resistance into parameters for successful stimulation, i.e. eliciting an action potential, are not available yet. Therefore, a method is proposed for the detection of active membrane currents, elicited by extracellular current stimulation. The method is based on the prediction of the linear part of the response to an applied stimulus current pulse using an impedance model of the neuron-electrode contact. Active membrane currents are detected in the nonlinear response, which is obtained by subtraction of the predicted linear response from the measured response. The required impedance model parameters are extracted from impedance spectroscopy or directly from the measured responses.

Measurement of sealing resistance of cell-electrode interfaces in neuronal cultures using impedance spectroscopy.

Sealing resistance is highly significant with respect to the electrical neuron-electrode contact because it decreases the stimulation threshold of neurons cultured on a planar micro-electrode array. A method is proposed for measurement of the sealing resistance using impedance spectroscopy. The effect of the sealing resistance on the total impedance spectrum of a cell-electrode interface is modelled for complete coverage of the electrode by the cell. Sensitivity analysis demonstrates that the impedance spectrum is determined by four parameters: two electrode parameters, the sealing resistance and the shunt capacitance between the lead of the electrode and the culture medium. Experimental verification of the model is performed by simultaneous measurement of the impedance spectrum and electrode coverage. A good and unique fit between the simulated and measured impedance spectra was obtained by varying the two electrode parameters and the sealing resistance.