Article

A Laser Stimulator for the Study of Cutaneous Thermal and Pain Sensations

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Abstract

A laser thermal stimulator system is described which enables the psychophysical and neurophysiological study of cutaneous thermal and pain sensations by means of a non-contact, precise stimulator. A carbon dioxide laser is used as the heat source with closed loop control of skin temperature via a sophisticated radiometer. Temperature steps of 0.1°C to 25°C have been achieved with rise rates of greater than 30°C/second. The temperature can be maintained to better than ±0.1°C over pulse durations of 0.3 seconds to 20 seconds.

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... light bulbs) lack the power to produce stepped heat stimuli for the recording of time-locked responses to the stimulus, such as reaction times or event-related brain potentials (ERPs). This was resolved in the mid seventies with the introduction of the CO 2 laser as a nociceptor stimulator by Carmon et al. (1976) and Meyer et al. (1976). The CO 2 laser offers the advantage of producing a collimated beam of monochromatic electromagnetic waves resulting in a high power density several orders of magnitude higher than any conventional light source. ...
... The second stimulator is power regulated with a temperature feedback control based on the measurement of the temperature of the skin at the site of stimulation (Laser Stimulation Device, SIFEC, Belgium) (Churyukanov et al., 2012). The conception of this laser was inspired by a similar feedback-controlled device developed by Meyer et al. (1976). The closed-loop control of laser power is performed by an online monitoring of skin temperature using a radiometer collinear with the laser beam, enabling to produce temperature steps with rise rates greater than 350 @BULLET C/s and pulse durations from 10 ms to 50 s. ...
Article
Thermal laser stimulation of the skin is an efficient exploratory tool to characterize the nociceptive system. In the present study, finite element simulations are done to calculate the intra-cutaneous spatio-temporal temperature profiles following the delivery of such laser stimuli. The proposed computer-aided modeling considers a number of important parameters that have been disregarded in previous approaches: (i) variability of water content across the skin in both hairy and glabrous skin, (ii) temperature dependency of optical and thermal skin parameters, (iii) laser wavelength and corresponding absorption coefficient, (iv) beam shape (Gaussian vs. flat top) and (v) power emission (closed vs. open loop). Numerical simulations allow determining at each instant of time the volume and area of skin tissue whose temperature exceeds a given nociceptor activation threshold. This knowledge allows a finer characterization of the subpopulations of primary afferents that encode and convey nociceptive signals to the central nervous system. As an example, the approach is used to obtain an estimate of intraepidermal nerve fiber density in both physiological and pathological conditions. Moreover, a better knowledge of the heat distribution also reduces the risk of injury to the skin. Finally, in order to make the finite element simulations accessible to investigators with no prior background in numerical analysis, a specific open-source user-interface has been developed with the ONELAB software.
... The stimuli were generated using a CO 2 laser stimulator with power that is regulated using a feedback control based on an online measurement of skin temperature at the site of stimulation (Laser Stimulation Device, SIFEC, Ferrière, Belgium) [6]. Conception of the laser was inspired by a similar feedback-controlled device developed by Meyer et al. (1976) [20]. Both devices are based on a closed-loop control of laser power by an online monitoring of skin temperature performed using a radiometer collinear with the laser beam. ...
... The stimuli were generated using a CO 2 laser stimulator with power that is regulated using a feedback control based on an online measurement of skin temperature at the site of stimulation (Laser Stimulation Device, SIFEC, Ferrière, Belgium) [6]. Conception of the laser was inspired by a similar feedback-controlled device developed by Meyer et al. (1976) [20]. Both devices are based on a closed-loop control of laser power by an online monitoring of skin temperature performed using a radiometer collinear with the laser beam. ...
Article
C‐fibre laser‐evoked potentials can be obtained reliably at single‐subject level from the hand and foot using a temperature‐controlled CO2 laser combined with an adaptive algorithm based on reaction times. ABSTRACT: Brain responses to the activation of C‐fibres are obtained only if the co‐activation of Aδ‐fibres is avoided. Methods to activate C‐fibres selectively have been proposed, but are unreliable or difficult to implement. Here, we propose an approach combining a new laser stimulator to generate constant‐temperature heat pulses with an adaptive paradigm to maintain stimulus temperature above the threshold of C‐fibres but below that of Aδ‐fibres, and examine whether this approach can be used to record reliable C‐fibre laser‐evoked brain potentials. Brief CO2 laser stimuli were delivered to the hand and foot dorsum of 10 healthy subjects. The stimuli were generated using a closed‐loop control of laser power by an online monitoring of target skin temperature. The adaptive algorithm, using reaction times to distinguish between late detections indicating selective activation of unmyelinated C‐fibres and early detections indicating co‐activation of myelinated Aδ‐fibres, allowed increasing the likelihood of selectively activating C‐fibres. Reliable individual‐level electroencephalogram (EEG) responses were identified, both in the time domain (hand: N2: 704 ± 179 ms, P2: 984 ± 149 ms; foot: N2: 1314 ± 171 ms, P2: 1716 ± 171 ms) and the time‐frequency (TF) domain. Using a control dataset in which no stimuli were delivered, a Receiver Operating Characteristics analysis showed that the magnitude of the phase‐locked EEG response corresponding to the N2‐P2, objectively quantified in the TF domain, discriminated between absence vs presence of C‐fibre responses with a high sensitivity (hand: 85%, foot: 80%) and specificity (hand: 90%, foot: 75%). This approach could thus be particularly useful for the diagnostic workup of small‐fibre neuropathies and neuropathic pain.
... A few studies have been conducted on non-contact and remote thermal displays to stimulate local parts of the skin in the workspace with no device worn. For a remote heating display, radiation-based localized and prompt heating methods using a laser and infrared rays have been proposed [20][21][22][23][24]. These methods can control the irradiation position by using optical systems composed of lenses and Galvano mirrors. ...
Article
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In this study, we achieved a noncontact tactile display that presents a pinpoint and instantaneous cooling sensation on the skin surface with no devices directly in contact with the users body. We employed ultrasound phased arrays to generate a focused ultrasound, which locally and instantaneously expedites the vaporization of room-temperature water mist floating near the surface of the user's skin, offering a sudden pinpoint cooling sensation. In this paper, we describe the physical configuration of the proposed method and show the measurement results, demonstrating how the users skin surface was cooled. During the experiments, we discovered that a part of the skin exposed to a focused ultrasound within the floating mist was selectively cooled with negligible delay. Our prototype system offers a cooling spot of approximately 15 mm in diameter, which causes a temperature decrease of 4.6 K in 1 s and 3.3 K in the first 0.5 s on a hand situated 500 mm away from the device. Additionally, the ultrasound-driven cooling spot can be controlled on the skin surface, which is felt as a cool moving spot. Such a position-free cooling system with a high spatiotemporal resolution will open the door to unprecedented practical tactile applications.
... Fibers with a conduction velocity <2 m/s were classified as C-and those between 2 and 20 m/s as Ad-fibers. The responsiveness to heat was tested by applying a heat stimulus (49˚C, 3 s from a base temperature of 38˚C for 3 s) to the middle of the RF using a feedback-controlled carbon dioxide laser (Meyer et al., 1976). Instantaneous frequencies of responses to this stimulus were three point median smoothed and then used to classify C fibers as quickly (QC) or slowly (SC) responding afferents as previously described (Wooten et al., 2014). ...
Article
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In humans, intradermal administration of β-alanine (ALA) and bovine adrenal medulla peptide 8-22 (BAM8-22) evokes the sensation of itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express the receptors of these pruritogens, MRGPRD and MRGPRX1, respectively, and which cutaneous afferents these pruritogens activate in primate. In situ hybridization studies revealed that MRGPRD and MRGPRX1 are co-expressed in a subpopulation of TRPV1+ human DRG neurons. In electrophysiological recordings in nonhuman primates (Macaca nemestrina), subtypes of polymodal C-fiber nociceptors are preferentially activated by ALA and BAM8-22, with significant overlap. When pruritogens ALA, BAM8-22, and histamine, which activate different subclasses of C-fiber afferents, are administered in combination, human volunteers report itch and nociceptive sensations similar to those induced by a single pruritogen. Our results provide evidence for differences in pruriceptive processing between primates and rodents, and do not support the spatial contrast theory of coding of itch and pain.
... Fibers with a conduction velocity <2 m/s were classified as C-and those between 2-20 m/s as Aδ-fibers. The responsiveness to heat was tested by applying a heat stimulus (49ºC, 3s from a base temperature of 38°C for 3s) to the middle of the RF using a feedback-controlled carbon dioxide laser (Meyer et al., 1976). Instantaneous frequencies of responses to this stimulus were 3 point median smoothed and then used to classify C fibers as quickly (QC) or slowly (SC) responding afferents as previously described (Wooten et al., 2014). ...
Preprint
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In human, intradermal administration of β-alanine (ALA) and bovine adrenal medulla peptide 8-22 (BAM8-22) evokes the sensation of itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express the receptors of these pruritogens, MRGPRD and MRGPRX1 respectively, and which cutaneous afferents these pruritogens activate in primate. In situ hybridization studies revealed that MRGPRD and MRGPRX1 are co-expressed in a subpopulation of TRPV1+ human DRG neurons. In electrophysiological recordings in nonhuman primates (Macaca nemestrina), subtypes of polymodal C-fiber nociceptors are preferentially activated by ALA and BAM8-22, with significant overlap. When pruritogens ALA, BAM8-22 and histamine, that activate different subclasses of C-fiber afferents, are administered in combination, human volunteers report itch and nociceptive sensations similar to those induced by a single pruritogen. Our results provide evidence for differences in pruriceptive processing between primates and rodents, and do not support the spatial contrast theory of coding of itch and pain.
... Thermal displays in mid-air haptics, such as methods that employ infrared lasers [5] and thermal radiation [6], have been proposed. A method that uses lasers can also display a tactile sensation similar to a mechanical tap when an elastic medium is attached to the skin [7]. ...
Chapter
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In a typical mid-air haptics system, focused airborne ultrasound provides vibrotactile sensations to localized areas on bare skin. Herein, a method for displaying heat sensations to hands where gloves are worn is proposed. The gloves employed in this study are commercially available gloves with sound absorption characteristics, such as cotton work gloves without any additional devices such as Peltier elements. The method proposed in this study can also provide vibrotactile sensations by changing the ultrasonic irradiation pattern. In this paper, we report basic experimental investigations on the proposed method. By performing thermal measurements, we evaluate the local heat generation on the surfaces of both the glove and the skin by focused airborne ultrasound irradiation. In addition, we performed perceptual experiments, thereby confirming that the proposed method produced both heat and vibrotactile sensations. Furthermore, these sensations were selectively provided to a certain extent by changing the ultrasonic irradiation pattern. These results validate the effectiveness of our method and its feasibility in mid-air haptics applications.
... Methods for thermal pain assessment improved around 1950 when James D. Hardy and colleagues introduced controlled infrared stimulation using halogen bulbs for radiation of heat ( Hardy et al., 1951;Hardy et al., 1952), which allowed more precise stimulus control. Later, feedback-controlled Peltier contact thermal stimulators (Kenshalo and Bergen, 1975), and energy or radiation-controlled laser stimulators (Mor and Carmon, 1975;Meyer et al., 1976) were introduced, making heat stimulation the favorite pain assessment methods for decades to the extent that assessment of heat pain became implicitly the concept of pain assessment in general. Altered heat pain thresholds can reflect either the function of myelinated Ad-fibers or unmyelinated C-fibers, depending on the rate, location, and sequence of stimulation (Collins et al., 1960;Price et al., 1989;Verdugo and Ochoa, 1992;Andersen et al., 1995;Koltzenburg et al., 1997). ...
Chapter
Synopsis Psychophysics emerged at the beginning of a rational experimenting approach to physiological and psychological science. Pain involves scaling of sensory events, necessitating multidimensional access to the full representation of pain as a sensory and affective event. This has an impact on comprehensive representation of pain in its somatosensory context, on mechanistic reasoning regarding physiological and pathological mechanisms.
... Thermal displays in mid-air haptics, such as methods that employ infrared lasers [5] and thermal radiation [6], have been proposed. A method that uses lasers can also display a tactile sensation similar to a mechanical tap when an elastic medium is attached to the skin [7]. ...
Preprint
In a typical mid-air haptics system, focused airborne ultrasound provides vibrotactile sensations to localized areas on a bare skin. Herein, a method for displaying thermal sensations to hands where mesh fabric gloves are worn is proposed. The gloves employed in this study are commercially available mesh fabric gloves with sound absorption characteristics, such as cotton work gloves without any additional devices such as Peltier elements. The method proposed in this study can also provide vibrotactile sensations by changing the ultrasonic irradiation pattern. In this paper, we report basic experimental investigations on the proposed method. By performing thermal measurements, we evaluate the local heat generation on the surfaces of both the glove and the skin by focused airborne ultrasound irradiation. In addition, we performed perceptual experiments, thereby confirming that the proposed method produced both thermal and vibrotactile sensations. Furthermore, these sensations were selectively provided to a certain extent by changing the ultrasonic irradiation pattern. These results validate the effectiveness of our method and its feasibility in mid-air haptics applications.
... Since a wide range of laser stimulators have been developed so far (most common ones described above: 1.4 Laser stimulation as a method to activate heat-gated ion channels), the results obtained from them have shown different aspects of the nociceptive pathway. Studies using laser stimulation to investigate single neuron properties in primary afferents have been performed extensively during recent decades 10,50,56,94,95,113,114,118,[127][128][129][130] . Bromm and colleagues measured microneurographic recordings of primary afferents in the radial nerve in response to laser-heat stimulation on the receptive fields of identified units and observed that the largest receptor class which was activated by CO 2 laser stimuli were polymodal Cnociceptors 114 . ...
Thesis
Noxious heat is a natural stimulus that activates peripheral sensory neurons expressing heat-gated ion channels. Recently, the TRPM3 channel emerged as a noxious heat sensor independent of TRPV1, which is also sensitive to the neurosteroid Pregnenolone sulphate (PS). Recently, evidence of a direct mechanism that controls the agonist-induced TRPM3 channel activity by activation of the µ-opioid receptor (MOR) has been described, through direct binding of the G-beta-gamma subunit to TRPM3. The submitted thesis investigated mechanisms of heat-induced nociception using near-infrared laser stimulation as a rapid and accurate way to apply noxious heat. Responses to laser-heat were analyzed: in vitro by functional assays on heterologous expression systems and primary culture of sensory neurons, and in vivo by behavioral experiments and electrophysiological recordings at the dorsal horn of the spinal cord. Laser-heat activates TRPV1 and TRPM3 channels in heterologous expression systems with activation thresholds of about 574 µJ and 615 µJ. The response amplitudes of TRPM3 upon activation with PS exceeded those of maximum laser stimulation (1.5 ± 0.003 of the ratio 340/380 versus 0.66 ± 0.011). Chemical- and thermal- induced activity of the TRPM3 channel co-expressing the MOR was reduced with DAMGO by 63.4% and 44.5%. In DRGs, 15-25% of all neurons analyzed (n= 550) functionally co-expressed TRPV1 and TRPM3, 38% expressed TRPV1 independent of TRPM3, 7-8% expressed TRPM3 but not TRPV1. DRG neurons displayed a direct inhibition by 18 ± 4.1% and 23 ± 3% when co-applying the MOR agonist DAMGO with PS. In the dorsal horn of the spinal cord, the processing of peripheral laser stimulation was carried out by a subset of WDR and HTM neurons, which were found at all depths of the dorsal horn (range: 120-820 µm). Laser-heat stimuli induced pain-behavior in vivo. All neurons that responded to suprathreshold laser-heat were nociceptive, including one third of WDR neurons and half of HTM neurons investigated. No laser-heat responses of LTM neurons were found. The peripheral input of the laser sensitive neurons was composed of C- and A- fibers; however, responses to laser-heat were transmitted by C-fibers. The sizes of the heat receptive fields ranged 10% - 60% of the mechanical receptive field and they located always inside them. The number of AP following laser stimulation was higher in HTM neurons compared to WDR neurons (14 ± 0.7 vs 9 ± 4.3), however not significant, and the latencies after onset of the laser stimulation were 266 ± 16 ms and 308.3 ± 55. The estimated temperature threshold for laser sensitive WDR neurons and HTM neurons (40.1 °C and 43.3 °C) was comparable to the mean heat withdrawal threshold in awake rats (41 °C). Differences in the proportions of neurons expressing TRPM3 and/or TRPV1 could be responsible for those differences in receptive field sizes. Since the threshold for laser-heat activation of the TRPM3 channel was higher than the threshold for TRPV1, a greater proportion of peripheral neurons containing TRPM3 might converge in dorsal horn laser sensitive HTM neurons than for laser sensitive WDR neurons.
... All participants received "high" (moderately painful), "medium" (pain threshold) and "low" (non-painful) intensity laser stimuli during the experiment. Laser stimuli were used due to their high selectivity to Adelta and C nociceptive fibers (Meyer et al., 1976), and were administered using a thulium laser with a beam diameter of 6 mm and pulse duration of 100 ms to the dorsal surface of the right forearm. The pulses were systematically moved around the skin surface to avoid skin sensitisation, damage, and habituation. ...
... All participants received "high" (moderately painful), "medium" (pain threshold) and "low" (nonpainful) intensity laser stimuli during the experiment. Laser stimuli were used due to their high selectivity to A-delta and C nociceptive fibers (Meyer et al., 1976), and were administered using a thulium laser with a beam diameter of 6 mm and pulse duration of 100 milliseconds to the dorsal surface of the right forearm. The pulses were systematically moved around the skin surface to avoid skin sensitisation, damage, and habituation. ...
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Chronic pain is exacerbated by maladaptive cognition such as pain catastrophizing (PC). Biomarkers of PC mechanisms may aid precision medicine for chronic pain. Here, we investigate EEG biomarkers using mass univariate and multivariate (machine learning) approaches. We test theoretical notions that PC results from a combination of augmented aversive-value encoding ("magnification") and persistent expectations of pain ("rumination"). Healthy individuals with high or low levels of PC underwent an experimental pain model involving nociceptive laser stimuli preceded by cues predicting forthcoming pain intensity. Analysis of EEG acquired during the cue and laser stimulation provided event-related potentials (ERPs) identifying spatially and temporally-extended neural representations associated with pain catastrophizing. Specifically, differential neural responses to cues predicting high vs. low intensity pain (i.e. aversive value encoding) were larger in the high PC group, largely originating from mid-cingulate and superior parietal cortex. Multivariate spatiotemporal EEG patterns evoked from cues with high aversive value selectively and significantly differentiated the high PC from low PC group (64.6% classification accuracy). Regression analyses revealed that neural patterns classifying groups could be partially predicted (R 2 = 28%) from those neural patterns classifying the aversive value of cues. In contrast, behavioural and EEG analyses did not provide evidence that PC modifies more persistent effects of prior expectation on pain perception and nociceptive responses. These findings support the hypothesis of magnification of aversive value encoding but not persistent expression of expectation in pain catastrophizers. Multivariate patterns of aversive value encoding provide promising biomarkers of maladaptive cognitive responses to chronic pain.
... Following each stimulus (occurring every 10 s), the laser beam was relocated to a different area of the forearm to minimize sensitization, habituation or damage to the skin. Previous studies have shown evidence of contactless activation of nociceptors related to Ad and C fibres using brief CO 2 laser stimuli (Meyer et al., 1976). All participants were obliged to wear safety goggles whenever the laser was in use. ...
Article
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Background: Acute noxious stimuli induce a suppression of cortical alpha activity, yet little is known about whether increasing alpha activity affects the processing of noxious stimuli. We have previously shown that visual alpha stimulation reduces experimental pain. Here, we demonstrate that increasing alpha power causes a reciprocal suppression of acute nociceptive processing. Methods: We attempted to increase cortical alpha activity through visual entrainment at 8 Hz, 10 Hz and 12 Hz to investigate the influence on the electrophysiological pain response. Moderately painful laser-heat stimuli were delivered following 10 minutes of visual entrainment across the alpha range. Results: Alpha power increased significantly relative to the 1 Hz control condition following 8 Hz and 10 Hz visual stimulation. Significant reductions in the P2 peak amplitude of the laser-evoked potential were found following visual entrainment at 10 Hz; the frequency stimulation resulting in the largest reduction in pain perception. Source analysis revealed that, following the 10 Hz stimulation, sources of increased alpha power and decreased nociceptive processing overlapped in precuneus and posterior cingulate cortex, with further reductions in nociceptive processing in insula cortex. Conclusions: As far as we are aware, this is the first study to provide direct evidence that experimental induction of increased alpha power suppresses the cortical processing of acute pain. Significance: While it is known that visual stimulation can increase the brain's oscillatory alpha rhythms, here, we show that this increase in alpha power occurs alongside reduced cortical processing of nociception, as measured with EEG. This establishes an objective marker of alpha entrainment-based analgesia that may be useful in the development of neuromodulatory treatments for clinical pain.
... The power output of this stimulator is regulated online using a feedback control loop based on a continuous measurement of skin temperature at the site of stimulation performed using a radiometer collinear with the laser beam (Laser Stimulation Device, SIFEC, Belgium). A similar feedback-controlled device developed by Meyer et al. (1976) inspired the conception of this laser. Because the radiometer used in the present device is capable of obtaining a reliable estimate of target temperature with a very short integration time, the feedback loop is able to update laser power output at a very fast rate (500 Hz). ...
Article
The recording of event-related brain potentials triggered by a transient heat stimulus is used extensively to study nociception and diagnose lesions or dysfunctions of the nociceptive system in humans. However, these responses are related exclusively to the activation of a specific subclass of nociceptive afferents: quickly-adapting thermonociceptors. In fact, except if the activation of Aδ fibers is avoided or if A fibers are blocked, these responses specifically reflect activity triggered by the activation of Type 2 quickly-adapting A fiber mechano-heat nociceptors (AMH-2). Here, we propose a novel method to isolate, in the human electroencephalogram (EEG), cortical activity related to the sustained periodic activation of heat-sensitive thermonociceptors, using very slow (0.2 Hz) and long-lasting (75 s) sinusoidal heat stimulation of the skin between baseline and 50 °C. In a first experiment, we show that when such long-lasting thermal stimuli are applied to the hand dorsum of healthy volunteers, the slow rises and decreases of skin temperature elicit a consistent periodic EEG response at 0.2 Hz and its harmonics, as well as a periodic modulation of the magnitude of theta, alpha and beta band EEG oscillations. In a second experiment, we demonstrate using an A fiber block that these EEG responses are predominantly conveyed by unmyelinated C fiber nociceptors. The proposed approach constitutes a novel mean to study C fiber function in humans, and to explore the cortical processing of tonic heat pain in physiological and pathological conditions.
... It has been demonstrated that a contactless activation of nociceptors related to Aδ and C fibres can be achieved through the use of a brief CO2 laser stimulus (Meyer et al., 1976). In this study, the pain stimulus consisted of a CO2 laser stimulus of 150ms duration and a beam diameter of 15mm. ...
Article
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Background: Alpha power is believed to have an inverse relationship with the perception of pain. Increasing alpha power through an external stimulus may, therefore, induce an analgesic effect. Here, we attempt to modulate the perception of a moderately painful acute laser stimulus by separately entraining three frequencies across the alpha band: 8, 10 and 12 Hz. Methods: Participants were exposed to either visual or auditory stimulation at three frequencies in the alpha-band range and a control frequency. We collected verbal pain ratings of laser stimuli from participants following 10 minutes of flashing LED goggle stimulation and 10 minutes of binaural beat stimulation across the alpha range. Alterations in sleepiness, anxiety and negative mood were recorded following each auditory or visual alpha-rhythm stimulation session. Results: A significant reduction in pain ratings was found after both the visual and the auditory stimulation across all three frequencies compared with the control condition. In the visual group, a significantly larger reduction was recorded following the 10-Hz stimulation than succeeding the 8- and 12-Hz conditions. Conclusions: This study suggests that a short presentation of auditory and visual stimuli, oscillating in the alpha range, have an analgesic effect on acute laser pain, with the largest effect following the 10-Hz visual stimulation. Pain reductions following stimulation in the alpha range are independent of sleepiness, anxiety, and negative moods. Significance: This study provides new behavioural evidence showing that visual and auditory entrainment of frequencies in the alpha-wave range can influence the perception of acute pain in humans.
... Because the CO 2 laser has a wavelength of 10.6 lm, 99% of the delivered energy was confined within the most superficial layer of the skin (< 100 lm beneath the skin surface), i.e. where most of the free nerve endings of nociceptors terminate (Meyer et al., 1976). The laser beam was conducted through a 10-m optical fibre. ...
Article
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Human studies have shown that heterotopic nociceptive conditioning stimulation (HNCS) applied to a given body location reduce the percept and brain responses elicited by noxious test stimuli delivered at a remote body location. It remains unclear to what extent this effect of HNCS relies on the spinal-bulbar-spinal loop mediating the effect of diffuse noxious inhibitory controls (DNIC) described in animals, and/or on top-down cortical mechanisms modulating nociception. Importantly, some studies have examined the effects of HNCS on the brain responses to nociceptive input conveyed by Aδ-fibers. In contrast, no studies have explored the effects of HNCS on the responses to selective nociceptive C-fiber input and non-nociceptive Aβ fiber input. In this study, we measured the intensity of perception and event related potentials (ERPs) to stimuli activating Aδ-, C- and Aβ-fibers, before, during and after HNCS, obtained by immersing one foot in painful cold water. We observed that (i) the perceived intensity of nociceptive Aδ- and C- stimuli was reduced during HNCS, (ii) the ERPs elicited by Aδ- and Aβ-, and C- stimuli were also reduced during HNCS. Importantly, because Aβ-ERPs are related to primary afferents that ascend directly through the dorsal columns without being relayed at spinal level, the modulation of these responses may not be explained by an influence of descending projections modulating the transmission of nociceptive input at spinal level. Therefore, our results indicate that, in humans, HNCS should be used with caution as a direct measure of DNIC-related mechanisms.This article is protected by copyright. All rights reserved.
... The order of PET and thermal pain threshold assessments were randomised between participants and occurred on different days within four weeks of each other. Acute pain was induced using a CO 2 laser (150ms duration, beam diameter of 15mm), which specifically activates nociceptors in the skin [43], applied ...
Article
The experience of pain in humans is modulated by endogenous opioids, but it is largely unknown how the opioid system adapts to chronic pain states. Animal models of chronic pain point to upregulation of opioid receptors in the brain, with unknown functional significance. We sought evidence for a similar relationship between chronic pain and opioid receptor availability in humans. Using Positron Emission Tomography (PET) and the radiotracer C-diprenorphine, patients with arthritis pain (n = 17) and healthy controls (n = 9) underwent whole-brain PET scanning to calculate parametric maps of opioid receptor availability. Consistent with the upregulation hypothesis, within the arthritis group greater opioid receptor availability was found in the striatum (including the caudate) of patients reporting higher levels of recent chronic pain, as well as regions-of-interest in the descending opioidergic pathway including the anterior cingulate cortex, thalamus and periaqueductal gray. The functional significance of striatal changes were clarified with respect to acute pain thresholds: data across patients and controls revealed that striatal opioid receptor availability was related to reduced pain perception. These findings are consistent with the view that chronic pain may upregulate opioid receptor availability in order to dampen pain. Lastly, patients with arthritis pain, compared to healthy controls, had overall less opioid receptor availability within the striatum specifically, consistent with the greater endogenous opioid binding that would be expected in chronic pain states. Our observational evidence points to the need for further studies to establish the causal relationship between chronic pain states and OpR receptor adaptation.
... However, a shorter 30s stimulus held at a high temperature (53 ºC or 55 ºC) will cause erythaema (minimal increase in permeability of dermal vessels) in human skin (LaMotte 1979) and also in guinea pig skin (Sevitt, 1964). In addition, high-intensity stimuli (53 ºC) of shorter duration (30s) can cause sensitisation to pain that is said to be mediated by AMHs (Meyer et al. 1976;LaMotte 1979). ...
... As one might except the concept of controlling such a proces is an area of intense theory and research. Previously a somewhat similar system to this have been developed [Meyer et al., 1976], using a CO 2 laser with all the disadvantages of that type laser, see chapter 3. If one wishes to control a certain process there are a number of approaches. ...
... Acute pain was induced with a CO 2 laser that specifically activates nociceptors in the skin (Meyer et al., 1976). Heat stimuli of duration 150 ms and a with a beam diameter of 15 mm were applied to the dorsal surface of the subject's right forearm. ...
Article
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Supraspinal processes in humans can have a top-down enhancing effect on nociceptive processing in the brain and spinal cord. Studies have begun to suggest that such influences occur in conditions such as fibromyalgia (FM), but it is not clear whether this is unique to FM pain or common to other forms of chronic pain, such as that associated with osteoarthritis (OA). We assessed top-down processes by measuring anticipation-evoked potentials and their estimated sources, just prior (< 500 ms) to laser heat pain stimulation, in 16 patients with FM, 16 patients with OA and 15 healthy participants, by using whole-brain statistical parametric mapping. Clinical pain and psychological coping factors (pain catastrophizing, anxiety, and depression) were well matched between the patient groups, such that these did not confound our comparisons between FM and OA patients. For the same level of heat pain, insula activity was significantly higher in FM patients than in the other two groups during anticipation, and correlated with the intensity and extent of reported clinical pain. However, the same anticipatory insula activity also correlated with OA pain, and with the number of tender points across the two patient groups, suggesting common central mechanisms of tenderness. Activation in the dorsolateral prefrontal cortex was reduced during anticipation in both patient groups, and was related to less effective psychological coping. Our findings suggest common neural correlates of pain and tenderness in FM and OA that are enhanced in FM but not unique to this condition.
... Temperature step increases were delivered by a feedbackcontrolled CO 2 -laser (Meyer et al., 1976) to the hairy skin of the dorsal hand and lateral aspect of the upper arm (two runs each: one on the left and one on the right side of the body). The sequence of the four runs was balanced for proximal/ distal and left/right stimulation. ...
... Von Frey probes were used to map the mechanical receptive field and to identify spots within the receptive field of highest mechanical sensitivity. A laser thermal stimulator (Meyer et al. 1976) was used to test heat sensitivity. A-fiber nociceptors were differentiated from low-threshold mechanoreceptors by their lack of response to blunt pressure. ...
... Briefly, acute pain was induced using a CO 2 laser stimulus that specifically activates nociceptors in the skin. 33 Heat stimuli of 150 ms duration and a beam diameter of 15 mm were applied to the dorsal surface of the participants' right forearm. Patients were not instructed to use any meditation techniques during the experiment, but were also not explicitly told not to meditate. ...
Article
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Objectives: Mindfulness-based pain management programs (MBPMs) aim to improve mental and physical health in individuals with chronic pain. In this study, we investigated whether improvement in mental health might require (1) reduction in the sensory pain experience and brain correlates of that experience, and/or (2) improved perceptions of the controllability of pain and corresponding brain activity related to cognitive control and emotional regulation. Methods: Twenty-eight patients with chronic pain were assessed and randomized into an intervention group (who attended an 8-wk MBPM) or a control group (treatment-as-usual), before being reassessed after 8 weeks. Outcome measures included clinical pain, perceived control over pain, mental and physical health, and mindfulness. Neural activity was measured during the anticipation and experience of acute experimental pain, using electroencephalography with source reconstruction. Results: Improvements were found in the MBPM group relative to the control group in mental health, which related to greater perceived control of pain, but not to reductions in clinical or experimental pain ratings. Anticipatory and pain-evoked event-related potentials to acute experimental pain were decreased, but sources of these event-related potentials were estimated to be in regions that modulate emotional responses rather than pain intensity. Mental health and perceived control outcomes correlated with reduced anticipatory deactivations of dorsolateral prefrontal and somatosensory cortices. Discussion: Increased activity in cognitive control regions of the brain during pain anticipation related to improved mental health and perceived control over pain, but not to decreased pain experience. Greater perceived control may therefore result from improved regulation of the emotional response to pain.
Article
Background Cutaneous laser stimulation has commonly been employed to investigate the thermal properties of the nociceptive system. The aim of this study was to investigate how a temperature‐controlled laser system improves the assessment of directional discrimination in the nociceptive system. Methods In total, twenty healthy volunteers participated in this study. To determine the directional discrimination threshold (stimulation length 50% correct, expressed in mm), thermal stimuli were delivered using a diode laser and the laser beam was perpendicularly displaced across the skin to give a linear stimulation in four different directions (distal, proximal, lateral and medial) and displacement lengths (3 for lateral‐medial and 5 for distal‐proximal). Two temperature control modes were used in the stimulation system, open‐loop and closed‐loop control. The subjects had to report the perceived stimulus direction, the degree of certainty regarding the perceived direction and the intensity of the perceived stimulus (0–10 numerical rating scale, 3: pain threshold). Results During closed‐loop control, the orientation of stimuli was discriminated significantly more accurately than during open‐loop control. During closed‐loop control, the directional discrimination threshold was 31.9 and 26.1 mm for distal‐proximal and lateral‐medial directed stimuli, respectively. A numerical rating scale was significantly higher for the lateral/medial directions. Moreover, the variability of the discrimination threshold is reduced in the closed‐loop control system. Conclusions The findings show that discrimination ability is better in the lateral‐medial directions compared to the distal‐proximal directions. This study indicates that using a system enabling closed‐loop temperature control, allows more robust probing of the temporo‐spatial mechanisms in the nociceptive system. Significance This study shows that a newly developed temperature‐controlled laser stimulation system enhances the possibilities to investigate the nociceptive temporo‐spatial integration, as shown by a less variable directional discrimination threshold. The results also show that different orthogonal directions are discriminated differently. This new method allows a better investigation of the combined temporal and spatial mechanisms in the nociceptive system.
Article
Thermal sensation is crucial to enhancing our comprehension of the world and enhancing our ability to interact with it. Therefore, the development of thermal sensation presentation technologies holds significant potential, providing a novel method of interaction. Traditional technologies often leave residual heat in the system or the skin, affecting subsequent presentations. Our study focuses on presenting thermal sensations with low residual heat, especially cold sensations. To mitigate the impact of residual heat in the presentation system, we opted for a non-contact method, and to address the influence of residual heat on the skin, we present thermal sensations without significantly altering skin temperature. Specifically, we integrated two highly responsive and independent heat transfer mechanisms: convection via cold air and radiation via visible light, providing non-contact thermal stimuli. By rapidly alternating between perceptible decreases and imperceptible increases in temperature on the same skin area, we maintained near-constant skin temperature while presenting continuous cold sensations. In our experiments involving 15 participants, we observed that when the cooling rate was $-$ 0.2 to $-$ 0.24 $^\circ$ C/s and the cooling time ratio was 30 to 50%, more than 86.67% of the participants perceived only persistent cold without any warmth.
Article
Background: Infrared laser stimulation is a valuable tool in pain research, its primary application being the recording of laser-evoked brain potentials (LEPs). Different types of laser stimulators, varying in their skin penetrance, are likely to have a large influence on the LEPs, when stimulating different skin types. The aim of this study was to investigate how LEPs depend on laser type and skin location. Methods: Two different laser stimulators (CO2 and Nd:YAP) were used to compare LEPs in healthy subjects. Stimuli were delivered to the hand dorsum and palm to investigate the effects of skin type on the evoked responses. Stimulus-evoked brain responses were recorded using EEG and perceived intensity ratings were recorded. Computational modelling was used to investigate the observed differences. Results: LEPs evoked by stimulation of the hairy skin were similar between CO2 and Nd:YAP stimulation. In contrast, LEPs elicited from the palm were markedly different and barely present for CO2 stimulation. There was a significant interaction between laser type and skin type (RM-ANOVA, p < 0.05) likely due to smaller CO2 LEPs in the palm. CO2 stimuli to the palm also elicited significantly lower perceived intensities. The computational model showed that the observed differences were explainable by the laser absorption characteristics and skin thickness affecting the temperature profile at the dermo-epidermal junction (DEJ). Conclusions: This study shows that LEP elicitation depends on the combination of laser penetrance and skin type. Low penetrance stimuli, from a CO2 laser, elicited significantly lower LEPs and perceived intensities in the palm. Significance: This study showed that the elicitation of laser-evoked potentials in healthy humans greatly depends on the combination of laser stimulator type and skin type. It was shown that high penetrance laser stimuli are capable of eliciting responses in both hairy and glabrous skin, whereas low penetrance stimuli barely elicited responses from the glabrous skin. Computational modelling was used to demonstrate that the results could be fully explained by the combination of laser type and skin thickness.
Article
This paper investigates the effects of thermal referral and tactile masking illusions to achieve localized thermal feedback on the upper body. Two experiments are conducted. The first experiment uses a 2D array of sixteen vibrotactile actuators (4 × 4) with four thermal actuators to explore the thermal distribution on the user's back. A combination of thermal and tactile sensations is delivered to establish the distributions of thermal referral illusions with different numbers of vibrotactile cues. The result confirms that localized thermal feedback can be achieved through cross-modal thermo-tactile interaction on the user's back of the body. The second experiment is conducted to validate our approach by comparing it with thermal-only conditions with an equal and higher number of thermal actuators in VR. The results show that our thermal referral with a tactile masking approach with a lesser number of thermal actuators achieves higher response time and better location accuracy than thermal-only conditions. Our findings can contribute to thermal-based wearable design to achieve greater user performance and experiences.
Article
Objective: Laser stimulators have been widely used in pain studies to selectively activate Aδ and C nociceptors without coactivation of mechanoreceptors. Temperature-controlled laser systems have been implemented with low-temperature variations during stimulations, however, these systems purely enabled stationary stimulation. This study aimed to implement, test and validate a new laser stimulation system that controls skin temperature by continuously adjusting laser output during stimulus movement to allow accurate investigation of tempo-spatial mechanisms in the nociceptive system. Approach: For validation, laser stimuli were delivered to the right forearm of eight healthy subjects using a diode laser. The laser beam was displaced across the skin to deliver a moving thermal stimulation to the skin surface. To test the function and feasibility of the system, different stimulation parameters were investigated involving two control modes (open-loop and closed-loop), three displacement velocities (5, 10 and 12 mm/s), two intensities (high 46 °C and low 42 °C), two stimulus lengths (20 and 100 mm) and two directions (distal and proximal). Main results: During closed-loop control, the stimulation error and variation of stimulation temperatures were significantly smaller than during open-loop control. The standard deviation of stimulation temperatures increased significantly with stimulation intensity and displacement length. Significance: This study showed that more accurate, less variable laser stimulations were delivered to the skin using closed-loop control during a movable stimulus. The more uniform skin temperature during stimuli is likely to ensure a more uniform nociceptor activation.
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Clinical neurophysiologic investigation of pain pathways in humans is based on specific techniques and approaches, since conventional methods of nerve conduction studies and somatosensory evoked potentials do not explore these pathways. The proposed techniques use various types of painful stimuli (thermal, laser, mechanical, or electrical) and various types of assessments (measurement of sensory thresholds, study of nerve fiber excitability, or recording of electromyographic reflexes or cortical potentials). The two main tests used in clinical practice are quantitative sensory testing and pain-related evoked potentials (PREPs). In particular, PREPs offer the possibility of an objective assessment of nociceptive pathways. Three types of PREPs can be distinguished depending on the type of stimulation used to evoke pain: laser-evoked potentials, contact heat evoked potentials, and intraepidermal electrical stimulation evoked potentials (IEEPs). These three techniques investigate both small-diameter peripheral nociceptive afferents (mainly Aδ nerve fibers) and spinothalamic tracts without theoretically being able to differentiate the level of lesion in the case of abnormal results. In routine clinical practice, PREP recording is a reliable method of investigation for objectifying the existence of a peripheral or central lesion or loss of function concerning the nociceptive pathways, but not the existence of pain. Other methods, such as nerve fiber excitability studies using microneurography, more directly reflect the activities of nociceptive axons in response to provoked pain, but without detecting or quantifying the presence of spontaneous pain. These methods are more often used in research or experimental study design. Thus, it should be kept in mind that most of the results of neurophysiologic investigation performed in clinical practice assess small fiber or spinothalamic tract lesions rather than the neuronal mechanisms directly at the origin of pain and they do not provide objective quantification of pain.
Article
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Los dolorímetros láser son un tipo de estimulador que se emplea para investigar clínicamente desórdenes de las fibras nerviosas Aδ y C. Ellos no se producen comercialmente. En el trabajo se analizan las principales insuficiencias de los dolorímetros láser reportados en la literatura. Se describe el dolorímetro láser Estimulas 2, con énfasis en su bloque de control. Se analizan los criterios técnicos aplicados al diseño de este dolorímetro, que permiten que esté libre de las deficiencias de dolorímetros anteriores. Se muestran los potenciales evocados láser por dolor obtenidos con este dolorímetro.
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A discussion of pain is apropos to a symposium that honors the career of Vernon Mountcastle. Professor Mountcastle served at one time as a mentor for us and has had a substantial influence on our research on pain sensibility. Though there are many aspects of Mountcastle’s influence that would be difficult to set down in specific terms, three themes stand out.
Article
Widespread hyperalgesia has been found in patients with painful hip osteoarthritis (OA) which can be normalized after total hip arthroplasty (THA) if patients have no residual postoperative pain. This study characterized the preoperative somatosensory profiles and provided possible interpretation of underlying pain mechanisms that might influence the development of postoperative pain. Forty hip OA patients with unilateral pain were assessed before and 6 weeks post-THA and compared with forty asymptomatic control subjects. Hip pain intensity at rest and while walking was assessed on a visual analogue scale (VAS). Bilateral cuff algometry from the thighs were used to assess the cuff pressure pain thresholds (cPPT), pressure values at VAS scores equal with 6 cm (PVAS6), cuff pressure tolerance (cPTT), and temporal summation of pain (TSP) quantified by an increase in VAS scores to repeated phasic cuff stimulations. Correlations between hip pain VAS post-THA and preoperative QST results were analyzed. Post-THA hip pain VAS scores decreased (P<0.05) compared to pre-THA. The cPPT, PVAS6, and cPTT were significantly lower bilaterally in both pre-THA and post-THA patients compared with controls (P<0.05). TSP was facilitated bilaterally in pre-THA patients compared with controls and normalized following THA in postoperative pain-free patients (P<0.05). Postoperative hip pain VAS scores correlated with preoperative ipsilateral TSP (r=0.44, P<0.05). Bilateral pressure pain hypersensitivity and facilitated TSP were demonstrated in preoperative hip OA patients. Although persistent postoperative pain is known as multifactorial, greater preoperative TSP was associated with greater pain and less reduction in pain after THA.
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Schmerzmessung (Algesimetrie) wendet im Grunde jeder Arzt an, der bei einer neurologischen Untersuchung mit der Nadel die Funktion des nozizeptiven Systems prüft. Diese klinische Untersuchungsmethode liefert allerdings nur qualitative Informationen. Für quantitative Aussagen, etwa über die Wirkung von Analgetika, braucht man ausgefeiltere algesimetrische Verfahren. Wenn das Ziel der Messung die Erfassung der Schmerzhaftigkeit ist, sprechen wir von „subjektiver Algesimetrie„, da eine subjektive, der Beobachtung des Untersuchers nicht unmittelbar zugängige Variable untersucht wird. Ein anderer Ansatz besteht darin, physiologische Meßgrößen als Maß für die Schmerzhaftigkeit heranzuziehen, um eine „objektive“, von der subjektiven Aussage des Patienten unabhängige Algesimetrie zu betreiben. Auch diese Art von Untersuchung wird im Grunde jedem Anästhesiologen vertraut sein, der z. B. die Analgesie bei einer Narkose an Hand des Blutdruckanstieges bei einer chirurgischen Manipulation abschätzt, oder die Fluchtreflexe untersucht, um die „Narkosetiefe“ zu bestimmen.
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Skin sensations are of three main types. First, there are sensations caused by innocuous mechanical stimuli, such as touch, pressure, vibration and tickle. Second, there are sensations of warmth and cold due to small, innocuous, temperature changes. Third, unpleasant sensations of pain or itch are caused by the presence of certain chemical agents in the skin or, in the case of pain, by potentially or actually damaging levels of thermal or mechanical stimuli. In addition, more complex sensory blends, such as wetness, also occur.
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Pain has two aspects. The first is its function as a warning system to ward off immediate threats. It is, in a sense, a necessary evil that serves to warn the organism of injury. But pain has another face, which we term hyperalgesia—the perceptual companion of inflammation, be it from infection, the mundane abrasion, a burn of the skin, or from the causalgia that mysteriously complicates only certain nerve injuries and cripples its victim. Save for the latter condition, where the pain seems to serve no apparent purpose, hyperalgesia seems not to be part of a warning system but instead is a reminder that something is wrong. A remarkable resetting of the threshold for pain occurs: the inflamed skin may become the source of increased pain merely by being lightly touched or gently warmed. The victim arduously protects the hyper-algesic part, which we infer may ultimately promote healing.
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The search for peripheral neural determinants of pain is aided by the attempt to correlate measurements of pain sensation with neural activity in peripheral afferent nerve fibers. Those fibers that respond only to noxious stimulation of their receptive fields are called “nociceptive afferents” and their distal endings, “nociceptors”. The word “nociceptive” is derived from the Latin word for “injury”; yet a biologically useful function of neural activity in nociceptive afferents may be to evoke pain in order to signal the threat of injury before it actually occurs (Burgess and Perl, 1973). Evidence for this comes from the close correlation between neural activity in nociceptive afferents in the peripheral nerve of conscious humans and simultaneous reports of pain during noxious stimulation of the skin (Torebjörk and Hallin, 1974; van Hees and Gybels, 1972). Heating the skin is an effective method of quantifying noxious stimulation. It is well known that the magnitude of pain, evoked by heating the skin, is determined to a large extent by the stimulus temperature. Much less is known about the temporal determinants of pain and the way is which the duration and frequency of heating interact with intensity to influence the magnitude of pain. I will describe our analyses of these variables in psychophysical studies in humans, and in studies of heat-sensitive nociceptors in the monkey.
Article
Edited by Larry R. Squire, the seventh volume of The History of Neuroscience in Autobiography is a collection of autobiographical essays by notable senior scientists who discuss the major events that shaped their discoveries and their influences, as well as the people who inspired them and helped shape their careers as neuroscientists. Each entry also includes a complete CV so that the interested reader may see their rise through the ranks as they achieved some of the highest honors in neuroscience. Contributors to the seventh volume include: Floyd E. Bloom, Joaquín Fuster, Michael S. Gazzaniga, Bertil Hille, Ivan Izquierdo, Edward Jones, Kresimir Krnjević, Nicole M. Le Douarin, Terje Lomo, Michael M. Merzenich, John Wilson Moore, Robert Y. Moore, Michael I. Posner, Peter H. Schiller, Gordon M. Shepherd, and Robert H. Wurtz.
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Human studies have shown that heterotopic nociceptive conditioning stimulation (HNCS) applied to a given body location reduce the percept and brain responses elicited by noxious test stimuli delivered at a remote body location. It remains unclear to what extent this effect of HNCS relies on the spinal-bulbar-spinal loop mediating the effect of diffuse noxious inhibitory controls (DNIC) described in animals, and/or on top-down cortical mechanisms modulating nociception. Importantly, some studies have examined the effects of HNCS on the brain responses to nociceptive input conveyed by Aδ-fibers. In contrast, no studies have explored the effects of HNCS on the responses to selective nociceptive C-fiber input and non-nociceptive Aβ fiber input. In this study, we measured the intensity of perception and event related potentials (ERPs) to stimuli activating Aδ-, C-and Aβ-fibers, before, during and after HNCS, obtained by immersing one foot in painful cold water. We observed that (i) the perceived intensity of nociceptive Aδ-and C-stimuli was reduced during HNCS, (ii) the ERPs elicited by Aδ-and Aβ-, and C-stimuli were also reduced during HNCS. Importantly, because Aβ-ERPs are related to primary afferents that ascend directly through the dorsal columns without being relayed at spinal level, the modulation of these responses may not be explained by an influence of descending projections modulating the transmission of nociceptive input at spinal level. Therefore, our results indicate that, in humans, HNCS should be used with caution as a direct measure of DNIC-related mechanisms.
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In primates, C-fibre polymodal nociceptors are broadly classified into two groups based on mechanosensitivity. Here we demonstrate that mechanically sensitive polymodal nociceptors that respond either quickly (QC) or slowly (SC) to a heat stimulus differ in responses to a mild burn, heat sensitization, conductive properties and chemosensitivity. Superficially applied capsaicin and intradermal injection of β-alanine, an MrgprD agonist, excite vigorously all QCs. Only 40% of SCs respond to β-alanine, and their response is only half that of QCs. Mechanically insensitive C-fibres (C-MIAs) are β-alanine insensitive but vigorously respond to capsaicin and histamine with distinct discharge patterns. Calcium imaging reveals that β-alanine and histamine activate distinct populations of capsaicin-responsive neurons in primate dorsal root ganglion. We suggest that histamine itch and capsaicin pain are peripherally encoded in C-MIAs, and that primate polymodal nociceptive afferents form three functionally distinct subpopulations with β-alanine responsive QC fibres likely corresponding to murine MrgprD-expressing, non-peptidergic nociceptive afferents.
Article
When applying noxious heat stimuli to human skin in the study of the pain system, one of the main problems is not to cause permanent damage. A better understanding of the temperature distribution and the propagation of heat, i.e. heat flux, in human skin is thus needed. In order to investigate these problems thoroughly, we have developed a 3-dimensional finite element model (FEM) 4-layer of human skin. The model is kept simple for better understanding of the boundary problems. The water content in each layer is used for determining the thermal properties. It is therefore not a homogenous structure. In this model the stratum corneum has been included with lower water content than in the epidermis. Simulations shows that the surface temperature reaches high levels whereas the temperature in the deeper structure is much lower. Thermal and optical constants found in the literature was applied. Heat propagation downwards and outwards from the source has been investigated to understand of the accumulation of energy in the boundary between two layers. Prediction of the heat flux at boundary between the epidermis and dermis shows that for repetitive stimulation there is a risk of exceeding the threshold temperature of 65 degrees Celsius for irreversible damage.
Article
The objective of this study was to determine the threshold for sensing a 3.8 μm laser on the skin. The identification of the skin sensation threshold for invisible lasers is useful in providing scientific guidance to the safety community regarding accidental skin exposures. Knowledge of the level of sensation of lasers might be used to show that sensation may not coincide with the exposure limits, and could in fact be orders of magnitude greater than limits. This type of information can be used in conjunction with studies performed on animals to help better define the minimum radiant exposure required to elicit minor skin changes. Future standards for skin exposure could potentially be based on sensation thresholds, if the difference between gross morphologic skin changes and sensation provide a sufficient safety margin. This study involved exposing ten volunteers on their calf to incrementally increasing energy from single 3.8 μm, 4 μs pulses with a spot size of approximately 4 cm2. The laser pulse was sensed by the subjects between an average of 2.3 and 3.1 J∕cm2, a level significantly above the maximum permissible exposure, but below which significant gross morphologic changes occur to the skin. Exposures greater than 2.4 J∕cm2 resulted in desiccation with concomitant separation of the superficial layer of epidermis in all subjects. Mild erythema presented within five minutes at exposures greater than 6.4 J∕cm2, resolving within 72 h.
Article
Cutaneous injection of the capsaicin analog NE-21610 (Procter and Gamble) produces analgesia to heat but not mechanical stimuli in humans. The present study examined whether pretreatment of the skin with NE-21610 prevents the development of hyperalgesia following heat injury. On the 1st day of testing, 7 volunteers received a 30-μl intradermal injection of vehicle to one volar forearm and 10 μg of NE-21610 to the other volar forearm. On the 2nd test day the subjects rated the intensity of pain to mechanical and heat stimuli before and after a burn (48°C, 120 sec) to each injection site. At the vehicle site, the pain evoked by the burn was rated as moderate to strong. In addition, primary hyperalgesia to heat and mechanical stimuli, secondary hyperalgesia to mechanical stimuli, and flare were observed after the burn. In contrast, the pain evoked by the burn at the NE-21610-treated site was rated as weak, and primary hyperalgesia to heat and mechanical stimuli did not develop. In addition, the area of flare at the drug-treated site was smaller than that observed at the vehicle site, and no secondary hyperalgesia to mechanical stimuli was observed. These data suggest that pretreatment with the capsaicin analog NE-21610 may attenuate the pain and hyperalgesia associated with injury.
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The Laser Hazards Bibliography consists of 3414 references in the open literature broken into subject categories which relate to general biological effects, the eye, the skin, laser safety, laser propagation in the atmosphere, and laser measurements.
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or more than 25 years, investigators from APL and the Johns Hopkins School of Medi-cine have collaborated on research aimed at understanding the neural mechanisms of pain sensation. This research is based on correlating results from studies of pain sensations in humans with results from studies of neural activity in anesthetized animals. One aspect of pain that has clinical importance is hyperalgesia—the enhanced pain to stimuli applied to the skin that develops after tissue injury and in certain diseases. We review here the neural mechanisms of hyperalgesia. Primary hyperalgesia, which develops at the site of tissue injury, is associated with an increased sensitivity of the peripheral nerve fi bers involved in pain. Secondary hyperalgesia, which develops in uninjured tissue surrounding the site of injury, exhibits symptoms similar to those seen in chronic pain patients and is caused by an enhanced neural responsiveness in the central nervous system.
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The sections in this article are:
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New methodologies to assess analgesic response in humans are needed to better integrate preclinical and clinical data. In the present study we examined the test-retest stability of an innovative radiant heat methodology compared with an electrical stimulation methodology. For the radiant heat task, a modified rodent tail flick apparatus was used. The latency for finger withdrawal was recorded. For the electrical stimulation tasks, subjects placed two fingers on two electrodes from which they received a brief series of increasingly intense electrical stimulations. Maximum stimulus intensity (in milliamps) delivered was recorded. On each of 4 test days, the subjects received five test trials with a 10-min interval between trials. All the subjects were tested twice on each apparatus in a counterbalanced design. Finger withdrawal latencies for the radiant heat task did not differ significantly across test trials or test days. Finger withdrawal scores for electrical stimulation increased significantly across test trials as well as test days. These data show that the radiant heat method generates consistent latencies across trials and days, whereas shock produces trends over time. The radiant heat task, which is convenient to operate and inexpensive to build, appears promising as a reliable test of pain threshold in humans.
Article
The infrared reflectance of water in the region 5000-300 cm-1 has been measured at near-normal incidence and at an incidence angle of 53°. On the basis of the measured values of spectral reflectance and the existing data on spectral transmittance, we have obtained values for the real and imaginary parts of the refractive index of water. The resulting values, which are presented in both graphical and tabular form, are compared with recent determinations by other investigators.
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A monograph which covers "… the traditional concepts of pain, the newer data respecting the phenomenology of pain,… " and an outline of a "… comprehensive theory of pain experience compatible with available information." 505-item bibliography. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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Peltier refrigerators are almost ideal transducers to provide the precise temperature control necessary for investigation of thermal sensitivity. The operation of Peltier refrigerators is briefly described and a circuit is presented which automatically controls the temperature of the refrigerator to within ±0.025°C of a predetermined value. Changes in the temperature of the refrigerator from 0.05 to 10°C can be obtained with less than a 2% error.
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Citation R. F. Leftwich, "Comparison of InSb and HgCdTe in a Real-Time Scanning Infrared Camera," Appl. Opt. 9, 1941_1-1942 (1970) http://www.opticsinfobase.org/ao/abstract.cfm?URI=ao-9-8-1941_1
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Hazards associated with laser radiation and radiation used as tool in biology and medicine
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A simulant with a suitable surface and the correct thermal inertia, β=kρc, meets the primary requirement of accepting heat at the same rate as the skin. For protected skin, a simulant with a blackened opaque surface, β<sup>½</sup>=0.035 cal·cm<sup>-2</sup>·sec<sup>-½</sup>·°C<sup>-1</sup>, and equivalent depth x/2√α=0.12 sec <sup> 1 2 </sup> (α=k/ρc) is suitable. Such simulants have been made of fused silica and of an epoxy resin filled with aluminum powder. The detector was a butt welded copper-constantan thermocouple, flattened to a thickness of 0.0015 cm, or a thermocouple of evaporated gold and bismuth films, ∼6000 Å thick. Results with water flow simulating blood flow in the skin indicate that an inert system simulates the response of skin rather well; if some adjustment must be made for varying blood flow it can be done experimentally or by calculation.
Some factors affecting heart motion and its measurement
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