Thermal Detection Thresholds of Aδ- and C-Fibre Afferents Activated by Brief CO2 Laser Pulses Applied onto the Human Hairy Skin

Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO2 laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C) and C-fibres (39.8±1.7°C). Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively

Biological inflammatory markers mediate the effect of preoperative pain-related behaviours on postoperative analgesics requirements

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Selective nociceptor activation in volunteers by infrared diode laser

<p>Abstract</p> <p>Background</p> <p>Two main classes of peripheral sensory neurons contribute to thermal pain sensitivity: the unmyelinated C fibers and thinly myelinated Aδ fibers. These two fiber types may differentially underlie different clinical pain states and distinctions in the efficacy of analgesic treatments. Methods of differentially testing C and Aδ thermal pain are widely used in animal experimentation, but these methods are not optimal for human volunteer and patient use. Thus, this project aimed to provide psychophysical and electrophysiological evidence that whether different protocols of infrared diode laser stimulation, which allows for direct activation of nociceptive terminals deep in the skin, could differentially activate Aδ or C fiber thermonociceptors in volunteers.</p> <p>Results</p> <p>Short (60 ms), high intensity laser pulses (SP) evoked monomodal "pricking" pain which was not enhanced by topical capsaicin, whereas longer, lower power pulses (LP) evoked monomodal "burning" pain which was enhanced by topical capsaicin. SP also produced cortical evoked EEG potentials consistent with Aδ mediation, the amplitude of which was directly correlated with pain intensity but was not affected by topical capsaicin. LP also produced a distinct evoked potential pattern the amplitude of which was also correlated with pain intensity, which was enhanced by topical capsaicin, and the latency of which could be used to estimate the conduction velocity of the mediating nociceptive fibers.</p> <p>Conclusions</p> <p>Psychophysical and electrophysiological data were consistent with the ability of short high intensity infrared laser pulses to selectively produce Aδ mediated pain and of longer pulses to selectively produce C fiber mediated thermal pain. Thus, the use of these or similar protocols may be useful in developing and testing novel therapeutics based on the differential molecular mechanisms underlying activation of the two fiber types (e.g., TRPV1, TRPV2, etc). In addition, these protocol may be useful in determining the fiber mediation of different clinical pain types which may, in turn be useful in treatment choice.</p

Automated PGP9.5 immunofluorescence staining: a valuable tool in the assessment of small fiber neuropathy?

BACKGROUND: In this study we explored the possibility of automating the PGP9.5 immunofluorescence staining assay for the diagnosis of small fiber neuropathy using skin punch biopsies. The laboratory developed test (LDT) was subjected to a validation strategy as required by good laboratory practice guidelines and compared to the well-established gold standard method approved by the European Federation of Neurological Societies (EFNS). To facilitate automation, the use of thinner sections. (16 µm) was evaluated. Biopsies from previously published studies were used. The aim was to evaluate the diagnostic performance of the LDT compared to the gold standard. We focused on technical aspects to reach high-quality standardization of the PGP9.5 assay and finally evaluate its potential for use in large scale batch testing. RESULTS: We first studied linear nerve fiber densities in skin of healthy volunteers to establish reference ranges, and compared our LDT using the modifications to the EFNS counting rule to the gold standard in visualizing and quantifying the epidermal nerve fiber network. As the LDT requires the use of 16 µm tissue sections, a higher incidence of intra-epidermal nerve fiber fragments and a lower incidence of secondary branches were detected. Nevertheless, the LDT showed excellent concordance with the gold standard method. Next, the diagnostic performance and yield of the LDT were explored and challenged to the gold standard using skin punch biopsies of capsaicin treated subjects, and patients with diabetic polyneuropathy. The LDT reached good agreement with the gold standard in identifying small fiber neuropathy. The reduction of section thickness from 50 to 16 µm resulted in a significantly lower visualization of the three-dimensional epidermal nerve fiber network, as expected. However, the diagnostic performance of the LDT was adequate as characterized by a sensitivity and specificity of 80 and 64 %, respectively. CONCLUSIONS: This study, designed as a proof of principle, indicated that the LDT is an accurate, robust and automated assay, which adequately and reliably identifies patients presenting with small fiber neuropathy, and therefore has potential for use in large scale clinical studies

Thoughts of Death Modulate Psychophysical and Cortical Responses to Threatening Stimuli

Existential social psychology studies show that awareness of one's eventual death profoundly influences human cognition and behaviour by inducing defensive reactions against end-of-life related anxiety. Much less is known about the impact of reminders of mortality on brain activity. Therefore we explored whether reminders of mortality influence subjective ratings of intensity and threat of auditory and painful thermal stimuli and the associated electroencephalographic activity. Moreover, we explored whether personality and demographics modulate psychophysical and neural changes related to mortality salience (MS). Following MS induction, a specific increase in ratings of intensity and threat was found for both nociceptive and auditory stimuli. While MS did not have any specific effect on nociceptive and auditory evoked potentials, larger amplitude of theta oscillatory activity related to thermal nociceptive activity was found after thoughts of death were induced. MS thus exerted a top-down modulation on theta electroencephalographic oscillatory amplitude, specifically for brain activity triggered by painful thermal stimuli. This effect was higher in participants reporting higher threat perception, suggesting that inducing a death-related mind-set may have an influence on body-defence related somatosensory representations

Laser-induced thermoelastic effects can evoke tactile sensations

Humans process a plethora of sensory information that is provided by various entities in the surrounding environment. Among the five major senses, technology for touch, haptics, is relatively young and has relatively limited applications largely due to its need for physical contact. In this article, we suggest a new way for non-contact haptic stimulation that uses laser, which has potential advantages such as mid-air stimulation, high spatial precision, and long working distance. We demonstrate such tactile stimulation can be enabled by laser-induced thermoelastic effects by means of physical and perceptual studies, as well as simulations. In the physical study, the mechanical effect of laser on a human skin sample is detected using low-power radiation in accordance with safety guidelines. Limited increases (&lt; similar to 2.5 degrees C) in temperature at the surface of the skin, examined by both thermal camera and the Monte Carlo simulation, indicate that laser does not evoke heat-induced nociceptive sensation. In the human EEG study, brain responses to both mechanical and laser stimulation are consistent, along with subjective reports of the non-nociceptive sensation of laser stimuli.close1