Ken Steffen Frahm

Activation of peripheral nerve fibers by electrical stimulation in the sole of the foot

BackgroundHuman nociceptive withdrawal reflexes (NWR) can be evoked by electrical stimulation applied to the sole of the foot. However, elicitation of NWRs is highly site dependent, and NWRs are especially difficult to elicit at the heel. The aim of the present study was to investigate potential peripheral mechanisms for any site dependent differences in reflex thresholds.ResultsThe first part of the study investigated the neural innervation in different sites of the sole of the foot using two different staining techniques. 1) Staining for the Nav1.7 antigen (small nociceptive fibers) and 2) the Sihler whole nerve technique (myelinated part of the nerve). No differences in innervation densities were found across the sole of the foot using the two staining techniques: Nav1.7 immunochemistry (small nociceptive fibers (1-way ANOVA, NS)) and the Sihler’s method (myelinated nerve fibers (1-way ANOVA, NS)). However, the results indicate that there are no nociceptive intraepidermal nerve fibers (IENFs) innervating the heel.Secondly, mathematical modeling was used to investigate to what degree differences in skin thicknesses affect the activation thresholds of Aδ and Aβ fibers in the sole of the foot. The modeling comprised finite element analysis of the volume conduction combined with a passive model of the activation of branching cutaneous nerve fibers. The model included three different sites in the sole of the foot (forefoot, arch and heel) and three different electrode sizes (diameters: 9.1, 12.9, and 18.3 mm). For each of the 9 combinations of site and electrode size, a total of 3000 Aβ fibers and 300 Aδ fibers was modeled. The computer simulation of the effects of skin thicknesses and innervation densities on thresholds of modeled Aδ and Aβ fibers did not reveal differences in pain and perception thresholds across the foot sole as have been observed experimentally. Instead a lack of IENFs at the heel decreased the electrical activation thresholds compared to models including IENFs.ConclusionsThe nerve staining and modeling results do not explain differences in NWR thresholds across the sole of the foot which may suggest that central mechanisms contribute to variation in NWR excitability across the sole of the foot.

Surface EMG crosstalk during phasic involuntary muscle activation in the nociceptive withdrawal reflex

The human nociceptive withdrawal reflex is typically assessed using surface electromyography (sEMG). Based on sEMG, the reflex receptive field (RRF) can be mapped. However, EMG crosstalk can cause erroneous results in the RRF determination. Single differential (SD) vs. double differential (DD) surface EMG were evaluated. Different electrode areas and inter‐electrode‐distances (IED) were evaluated. The reflexes were elicited by electrical stimulation of the sole of the foot. EMG was obtained from both tibialis anterior (TA) and soleus (SOL) using both surface and intramuscular EMG (iEMG). The amount of crosstalk was significantly higher in SD recordings than in DD recordings (P < 0.05). Crosstalk increased when electrode measuring area increased (P < 0.05) and when IED increased (P < 0.05). Reflex detection sensitivity decreases with increasing measuring area and increasing IED. These results stress that for determination of RRF and similar tasks, DD recordings should be applied. Muscle Nerve 46: 228–236, 2012

Nerve Fiber Activation During Peripheral Nerve Field Stimulation: Importance of Electrode Orientation and Estimation of Area of Paresthesia.

Low back pain is one of the indications for using peripheral nerve field stimulation (PNFS). However, the effect of PNFS varies between patients; several stimulation parameters have not been investigated in depth, such as orientation of the nerve fiber in relation to the electrode. While placing the electrode parallel to the nerve fiber may give lower activation thresholds, anodal blocking may occur when the propagating action potential passes an anode.

Distinct temporal filtering mechanisms are engaged during dynamic increases and decreases of noxious stimulus intensity

Abstract Physical stimuli are subject to pronounced temporal filtering during afferent processing such that changes occurring at certain rates are amplified and others are diminished. Temporal filtering of nociceptive information remains poorly understood. However, the phenomenon of offset analgesia, where a disproportional drop in perceived pain intensity is caused by a slight drop in noxious heat stimulation, indicates potent temporal filtering in the pain pathways. To develop a better understanding of how dynamic changes in a physical stimulus are constructed into an experience of pain, a transfer function between the skin temperature and the perceived pain intensity was modeled. Ten seconds of temperature-controlled near-infrared (970 nm) laser stimulations above the pain threshold with a 1°C increment, decrement, or constant temperature were applied to the dorsum of the hand of healthy human volunteers. The skin temperature was assessed by an infrared camera. Offset analgesia was evoked by laser heat stimulation. The estimated transfer functions showed shorter latencies when the temperature was increased by 1°C (0.53 seconds [0.52-0.54 seconds]) than when decreased by 1°C (1.15 seconds [1.12-1.18 seconds]) and smaller gains (increase: 0.89 [0.82-0.97]; decrease: 2.61 [1.91-3.31]). The maximal gain was observed at rates around 0.06 Hz. These results show that temperature changes occurring around 0.06 Hz are best perceived and that a temperature decrease is associated with a larger but slower change in pain perception than a comparable temperature increase. These psychophysical findings confirm the existence of differential mechanisms involved in temporal filtering of dynamic increases and decreases in noxious stimulus intensity.

Analysis of muscle fiber conduction velocity enables reliable detection of surface EMG crosstalk during detection of nociceptive withdrawal reflexes

BackgroundThe nociceptive withdrawal reflex (NWR) is a polysynaptic spinal reflex that induces complex muscle synergies to withdraw a limb from a potential noxious stimulus. Several studies indicate that assessment of the NWR is a valuable objective tool in relation to investigation of various pain conditions. However, existing methodologies for NWR assessment evaluate standard surface electromyography (sEMG) measured over just one muscle and do not consider the possible interference of crosstalk originating from adjacent active muscles. The present study had two aims: firstly, to investigate to which extent the presence of crosstalk may affect NWR detection using a standardized scoring criterion (interval peak z-score) that has been validated without taking crosstalk into consideration. Secondly, to investigate whether estimation of muscle fiber conduction velocity can help identifying the propagating and non-propagating nature of genuine reflexes and crosstalk respectively, thus allowing a more valid assessment of the NWR.ResultsEvaluation of interval peak z-score did apparently allow reflex detection with high sensitivity and specificity (0.96), but only if the influence of crosstalk was ignored. Distinction between genuine reflexes and crosstalk revealed that evaluation of interval peak z-score incorporating a z-score threshold of 12 was associated with poor reflex detection specificity (0.26-0.62) due to the presence of crosstalk. Two different standardized methods for estimation of muscle fiber conduction velocity were employed to demonstrate that significantly different muscle fiber conduction velocities may be estimated during genuine reflexes and crosstalk, respectively. This discriminative feature was used to develop and evaluate a novel methodology for reflex detection from sEMG that is robust with respect to crosstalk. Application of this conduction velocity analysis (CVA) entailed reflex detection with excellent sensitivity (1.00 and 1.00) and specificity (1.00 and 0.96) for the tibialis anterior and soleus muscles.ConclusionThis study investigated the negative effect of electrical crosstalk during reflex detection and revealed that the use of a previously validated scoring criterion may result in poor specificity due to crosstalk. The excellent performance of the developed methodology in the presence of crosstalk shows that assessment of muscle fiber conduction velocity allows reliable detection of EMG crosstalk during reflex detection.

Muscle Activation During Peripheral Nerve Field Stimulation Occurs Due to Recruitment of Efferent Nerve Fibers, Not Direct Muscle Activation

Peripheral nerve field stimulation (PNFS) is a potential treatment for chronic low‐back pain. Pain relief using PNFS is dependent on activation of non‐nociceptive Aβ‐fibers. However, PNFS may also activate muscles, causing twitches and discomfort. In this study, we developed a mathematical model, to investigate the activation of sensory and motor nerves, as well as direct muscle fiber activation.

Tempo-spatial discrimination is lower for noxious stimuli than for innocuous stimuli

Abstract The exteroceptive sensory system is responsible for sensing external stimuli in relation to time and space. The aim of this study was to investigate the tempo-spatial properties of the exteroceptive system using painful laser heat and nonpainful mechanical touch stimulation. Thirteen healthy subjects were stimulated on the volar forearm using 2 paradigms: a continuous stimulation along a line on the skin and a 2-point stimulation. The line stimulations were delivered in both the distal and proximal direction with lengths of 25, 50, 75, and 100 mm. The 2-point stimulations were assessed by simultaneous stimuli at a point-to-point distance ranging from 10 to 100 mm, in steps of 10 mm. The subjects reported the intensity (0-10 numeric rating scale, 3: pain threshold) and either direction (line stimuli) or number of perceived points (2-point stimuli). All mechanical line stimulations were reported correctly, ie, a directional discrimination threshold of less than 25 mm. For painful laser line stimulation, the directional discrimination threshold was 68.5 and 70.2 mm for distally and proximally directed stimuli, respectively. The 2-point discrimination threshold for painful laser stimulation (67.9 mm) was higher than for the mechanical stimulation (34.5 mm). Numeric rating scale increased both with line length and distance between the 2 points (linear mixed model, P < 0.001). The findings indicate that the tempo-spatial acuity of the exteroceptive system is lower for noxious stimuli than for innocuous stimuli. This is possible due to the larger receptive fields of nociceptive neurons and/or less lateral inhibition.

Tempo-spatial discrimination to non-noxious stimuli is better than for noxious stimuli

Abstract Aims The exteroceptive sensory system is responsible for sensing external stimuli in relation to time and space. The aim of the study was to investigate the tempo-spatial properties of the exteroceptive system using laser heat and mechanical touch stimulation. Methods 13 healthy subjects were stimulated in the volar forearm. Each subject was stimulated using two paradigms, a continuous stimulation along a continuous line on the skin, and a simultaneous 2-point stimulation. The line stimulations were delivered in both a distal and proximal direction with lengths of 25, 50, 75, and 100 mm. The 2-point stimulations were delivered with a point-to-point distance ranging from 10 to 100 mm, in steps of 10 mm. Both paradigms were delivered using painful heat (laser) stimulation and mechanical (touch) stimulation. Following each stimulation, subjects had to report the intensity (0–10 NRS, 3 being pain threshold) and either direction (line stimuli) or number of perceived points (2-point stimuli). Results All four line lengths and both directions were reported correctly for all mechanical line stimulation (an accuracy of 100%). For laser line stimulation the directional discrimination threshold was 68.5 mm and 70.2 mm for distal and proximal directed stimuli, respectively. The 2-point discrimination threshold for heat stimulation (67.9 mm) was higher than for the mechanical stimulation (34.5 mm). NRS was significant higher for laser stimulations than for the mechanical stimulation for both line and 2-point stimulations. NRS increased both with line length and distance between the two points (ANOVA, p < 0.001). The average NRS was 3.15 and 0.91 for laser line and mechanical line stimulations, respectively. For 2-point stimulation the average NRS was 3.72 and 1.06 for laser and mechanical stimulations, respectively. Conclusions The findings indicate that the tempo-spatial acuity of the exteroceptive system is lower for noxious stimuli than for innoxious stimuli. This is possible due to the larger receptive fields of nociceptive neurons and/or less lateral inhibition.

Membrane properties in small cutaneous nerve fibers in humans.

Introduction: Assessment of membrane properties is important for understanding the mechanisms of painful peripheral neuropathy, developing new diagnostic techniques, and screening/profiling of analgesics that target ion channels. Methods: Small cutaneous nerves were activated electrically by small diameter (0.2 mm) cathodes, and large nerves were activated by ordinary patch electrodes. This new perception threshold tracking method combines perception threshold assessment and stimulation paradigms from conventional threshold tracking. Results: The strength‐duration time‐constant of large fibers (580 µs ± 160 µs) was lower than the time constant of small fibers (1060 µs ± 690 µs; P < 0.01, paired t‐test). Threshold electrotonus showed similar threshold reductions to sub‐threshold prepulses, except for 80 ms hyperpolarizing prepulses, to which small fibers showed less threshold reduction than large fibers (repeated‐measures analysis of variance, Bonferroni, P = 0.006). Conclusions: This is a reliable method to investigate the membrane properties of small cutaneous nerve fibers in humans and may be used in clinical settings as a diagnostic or profiling tool. Muscle Nerve 55: 195–201, 2017

Nerve Fiber Activation During Peripheral Nerve Field Stimulation: Importance of Electrode Orientation and Estimation of Area of Paresthesia: Modeling Optimal Nerve Fiber Activation During PNFS

Low back pain is one of the indications for using peripheral nerve field stimulation (PNFS). However, the effect of PNFS varies between patients; several stimulation parameters have not been investigated in depth, such as orientation of the nerve fiber in relation to the electrode. While placing the electrode parallel to the nerve fiber may give lower activation thresholds, anodal blocking may occur when the propagating action potential passes an anode.