Exploring Psychophysical and Neurophysiological Responses to Intra-Epidermal Electrical Stimuli in Patients With Persistent Spinal Pain Syndrome Type 2 with a Spinal Cord Stimulator

There is a lack of measures that provide insights into how spinal cord stimulation (SCS) modulates nociceptive function in patients with persistent spinal pain syndrome type 2 (PSPS-T2). Recently, we observed altered nociceptive detection thresholds (NDTs) in response to intra-epidermal electrical stimulation (IES) on the feet of PSPS-T2 patients when dorsal root ganglion stimulation was turned on. Furthermore, we observed altered NDTs and evoked potentials (EPs) in response to IES on the hands of PSPS-T2 patients. To explore whether EPs were obstructed by SCS artifacts, we applied IES twice to the hands of patients with SCS turned on (SCS-ON/ON group). To explore possible confounding effects of SCS outside the stimulated area, we repeated IES on the hands of these patients, once with SCS turned off and subsequently once with SCS turned on (SCS-OFF/ON group). The results demonstrated that EPs were not obstructed by SCS artifacts. Additionally, NDTs and EPs did not significantly change between measurements in the SCS-ON/ON and the SCS-OFF/ON groups. Therefore, the results suggested that possible confounding effects of SCS outside the nociceptive system did not interfere with the detection task performance. This work warrants further exploration of NDT-EP phenomena in response to IES at the painful feet of patients.Clinical Relevance—This work contributes to developing a clinical tool to explore psychophysical and neurophysiological biomarkers for observing modulating effects of SCS in patients with PSPS-T2

Identification of Diabetic Small-Fiber Neuropathy Based on Electrophysiological and Psychophysical Responses to Intra-Epidermal Electric Stimulation using a Naïve Bayes Classifier

Diagnosis and stratification of small-fiber neuropathy patients is difficult due to a lack of methods that are both sensitive and specific. Our lab recently developed a method to accurately measure psychophysical and electrophysiological responses to intra-epidermal electric stimulation, specifically targeting small nerve fibers in the skin. In this work, we study whether using one or a combination of psychophysical and electrophysiological outcome measures can be used to identify diabetic small-fiber neuropathy. It was found that classification of small-fiber neuropathy based on psychophysical and electrophysiological responses to intra-epidermal electric stimulation could match or even outperform current state-of-the-art methods for the diagnosis of small-fiber neuropathy.Clinical Relevance - Neuropathy is damage or dysfunction of nerves in the skin, often leading to the development of chronic pain. Small-fiber neuropathy is the most prevalent type of neuropathy and occurs frequently in patients with diabetes mellitus, but can also occur in other diseases or in response to chemotherapy. Early detection of neuropathy could help diabetic patients to adapt glucose management, and doctors to adjust treatment strategies to prevent nerve loss and chronic pain, but is impeded by a lack of clinical tools to monitor small nerve fiber function.</p

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.</p

Observing Altered Nociceptive Detection Thresholds in Patients With Persistent Spinal Pain Syndrome Type 2 With a Dorsal Root Ganglion Stimulator

Objectives: There is a lack of clinically relevant measures for quantification of maladaptive mechanisms of the nociceptive system leading to chronic pain. Recently, we developed a method that tracks nociceptive detection thresholds (NDTs) using intraepidermal electrical stimulation. In this study, we explored the feasibility of using this NDT method in patients with persistent spinal pain syndrome type 2 (PSPS-T2) and its potential to enable observation of altered nociceptive processing induced by dorsal root ganglion (DRG) stimulation. In addition, we compared NDTs with quantitative sensory testing (QST) measurements and numeric rating scale (NRS). Materials and Methods: A total of 12 patients with PSPS-T2 (seven men; 60.4 ± 12.3 years) experiencing chronic unilateral lower limb pain treated with DRG stimulation were included in the study. Both the NDT method and electrical and pressure QST methods were performed twice in the L5 dermatome on both the affected and the unaffected foot, once with the DRG stimulator turned off and, subsequently, once with the DRG stimulator turned on. Results: The NDT method can be applied to patients with PSPS-T2. With the DRG stimulator turned off, NDTs on the affected side were significantly higher than on the unaffected side. This difference was no longer present once the DRG stimulator was turned on. Furthermore, DRG stimulation affected QST (electrical and pressure) values and NRS scores. Finally, NDTs showed larger contrasts between the sides than QST measures. Conclusions: The NDT method permitted observation of altered nociceptive function. The effect of DRG stimulation also was reflected in QST outcomes and NRS scores. The larger contrast between the sides for NDTs suggests that the NDT method might be valuable for future quantification of nociceptive dysfunction in chronic pain