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.

BackgroundCO2 lasers have been used for several decades as an experimental non-touching pain stimulator. The laser energy is absorbed by the water content in the most superficial layers of the skin. The deeper located nociceptors are activated by passive conduction of heat from superficial to deeper skin layers.MethodsIn the current study, a 2D axial finite element model was developed and validated to describe the spatial temperature distribution in the skin after infrared CO2 laser stimulation. The geometry of the model was based on high resolution ultrasound scans. The simulations were compared to the subjective pain intensity ratings from 16 subjects and to the surface skin temperature distributions measured by an infrared camera.ResultsThe stimulations were sensed significantly slower and less intense in glabrous skin than they were in hairy skin (MANOVA, p < 0.001). The model simulations of superficial temperature correlated with the measured skin surface temperature (r > 0.90, p < 0.001). Of the 16 subjects tested; eight subjects reported pricking pain in the hairy skin following a stimulus of 0.6 J/cm2 (5 W, 0.12 s, d1/e2 = 11.4 mm) only two reported pain to glabrous skin stimulation using the same stimulus intensity. The temperature at the epidermal-dermal junction (depth 50 μm in hairy and depth 133 μm in glabrous skin) was estimated to 46°C for hairy skin stimulation and 39°C for glabrous skin stimulation.ConclusionsAs compared to previous one dimensional heat distribution models, the current two dimensional model provides new possibilities for detailed studies regarding CO2 laser stimulation intensity, temperature levels and nociceptor activation.

Offset analgesia could be activated with a feedback-controlled near-infrared laser system. Larger and delayed response to temperature decrease than to temperature increase was observed.

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.

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.