Exploring Nociceptive Detection Thresholds Combined with Evoked Potentials in Patients with Diabetes Mellitus

Abstract

There is a lack of diagnostic tools that can objectively measure small fiber neuropathy (SFN) in patients with diabetes mellitus (DM). Recently, nociceptive nerve function was observed by nociceptive detection thresholds (NDTs) and brain evoked potentials (EPs) during intraepidermal electrical stimulation (IES) targeting Aδ-fibers. In this proof of principle, we studied whether it is possible to measure NDTs combined with EPs in DM patients with and without neuropathic pain. Furthermore, we explored the sensitivity of NDTs and EPs for polyneuropathy in these patients. Five DM patients diagnosed with painful neuropathy (DMp), five DM patients without painful neuropathy (DM), and five healthy controls (HC) were analyzed. These preliminary results showed that we can accurately measure NDTs and EPs in patients with diabetes. Strikingly, increased NDTs were found in DM and DMp compared to HC, of which the DMp showed the largest NDTs. This suggests that NDTs during IES could be a powerful biomarker for monitoring peripheral dysfunctions. Current EEG data of patients did not show any significant differences. The population needs to be enlarged before we can investigate the sensitivity of these NDTs and EPs to diabetic polyneuropathy and associated changes in nociceptive processing in more detail. Clinical Relevance-This proof of principle in a small group of patients with diabetes mellitus potentially treats the observation of the loss of nociceptive function occurring with small fiber neuropathy. That helps the development of a diagnostic measure to monitor future (early-stage) nociceptive dysfunctions in a clinical environment.

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

“…As compared to age-and sex matched HC, in RA patients we observed higher NDTs to both single-and double pulse stimuli, and lower slopes to SP stimuli. Other studies in patient groups with the same method have been able to make similar observations, yet with a lower slope in response to both the single-and double pulse stimuli [17,18]. While more research is required to understand these differences, factors which are known to contribute differentially to the SP slope as compared to the DP slope, are the peripheral-and central sensitivity of the nociceptive function [10], as well as the internal criterion [26].…”

“…This is in contrast to PT measurements, which -upon strictly following a test protocol -are widely thought to predominantly reflect characteristics of nociceptive (dis)function that are relevant for the development and maintenance of chronic pain syndromes [22]. In multiple studies which have evaluated NDTs, interesting and relevant results using pain models [11][12][13][14][15]23] or patient groups [16][17][18][19]24] are obtained, but few studies have yet evaluated factors affecting the NDT outcomes. One factor which is well-known to affect the outcomes of NDT measurements, is the electrocutaneous interface [25].…”

“…One factor which is well-known to affect the outcomes of NDT measurements, is the electrocutaneous interface [25]. In fact, many of the cited studies use pain models which affect the integrity (e.g., capcaisin) or functioning (e.g., lidocaine) of the cutaneous nociceptive fibers, or have included patient groups in which the peripheral nociceptive fibers are affected [11,12,16,17,19]. As such, these studies provide evidence for NDTs to be sensitive to peripheral mechanisms.…”

“…NDTs have been evaluated and often also shown effects in multiple studies in which human pain models are used, such as capcaisin [11], lidocaine [12], sleep deprivation [13], a cold pressor test (CPT) [14] and high frequency stimulation (HFS) [15]. Lately, NDTs have also been successfully evaluated in a clinical setting such as in patients with small fiber neuropathy [16], (painful) diabetic neuropathy [17], failed back surgery syndrome [18], or neuropathic pain [19], whereby often higher NDTs were observed in the patient groups. These findings indicate that NDTs can measure characteristics of the nociceptive system, of which it is at present unknown to what extent these characteristics are relevant for the development and maintenance of chronic pain syndromes.…”

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

“…Previous laboratory experiments used IES of the dorsum of the hands (i.e., C7 dermatome) in healthy subjects [14,15]. Hence, clinical feasibility studies explored NDT-EP phenomena using IES performed on (non-painful) hands of patients (e.g., with PSPS-T2), which showed altered task performance compared to pain-free controls [16,17]. However, it is uncertain whether altered detection task performance in patients was related to nociceptive dysfunction.…”