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  • 1.
    Ng, Kevin
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Lafee, Odai Waleed Mohammad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Bouchatta, Otmane
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Makdani, Adarsh D.
    Liverpool John Moores Univ, England.
    Marshall, Andrew G.
    Univ Liverpool, England.
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Mcintyre, Sarah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Human Foot Outperforms the Hand in Mechanical Pain Discrimination2024In: eNeuro, E-ISSN 2373-2822, Vol. 11, no 2, article id 0412232024Article in journal (Refereed)
    Abstract [en]

    Tactile discrimination has been extensively studied, but mechanical pain discrimination remains poorly characterized. Here, we measured the capacity for mechanical pain discrimination using a two-alternative forced choice paradigm, with force-calibrated indentation stimuli (Semmes-Weinstein monofilaments) applied to the hand and foot dorsa of healthy human volunteers. In order to characterize the relationship between peripheral nociceptor activity and pain perception, we recorded single-unit activity from myelinated (A) and unmyelinated (C) mechanosensitive nociceptors in the skin using microneurography. At the perceptual level, we found that the foot was better at discriminating noxious forces than the hand, which stands in contrast to that for innocuous force discrimination, where the hand performed better than the foot. This observation of superior mechanical pain discrimination on the foot compared to the hand could not be explained by the responsiveness of individual nociceptors. We found no significant difference in the discrimination performance of either the myelinated or unmyelinated class of nociceptors between skin regions. This suggests the possibility that other factors such as skin biophysics, receptor density or central mechanisms may underlie these regional differences.

  • 2.
    Thorell, Oumie
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. School of Medicine, Western Sydney University, Sydney, NSW, Australia.
    Ydrefors, Johannes
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Svantesson, Mats
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Mahns, David A.
    School of Medicine, Western Sydney University, Sydney, NSW, Australia.
    Nagi, Saad S.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. School of Medicine, Western Sydney University, Sydney, NSW, Australia.
    Investigations into an overlooked early component of painful nociceptive withdrawal reflex responses in humans2023In: Frontiers in Pain Research, E-ISSN 2673-561X, Vol. 3, article id 1112614Article in journal (Refereed)
    Abstract [en]

    Introduction: The role of pain as a warning system necessitates a rapid transmission of information from the periphery for the execution of appropriate motor responses. The nociceptive withdrawal reflex (NWR) is a physiological response to protect the limb from a painful stimulus and is often considered an objective measure of spinal nociceptive excitability. The NWR is commonly defined by its latency in the presumed Aδ-fiber range consistent with the canonical view that "fast pain" is signaled by Aδ nociceptors. We recently demonstrated that human skin is equipped with ultrafast (Aβ range) nociceptors. Here, we investigated the short-latency component of the reflex and explored the relationship between reflex latency and pain perception.

    Methods: We revisited our earlier work on NWR measurements in which, following convention, only reflex responses in the presumed Aδ range were considered. In our current analysis, we expanded the time window to search for shorter latency responses and compared those with pain ratings.

    Results: In both cohorts, we found an abundance of recordings with short-latency reflex responses. In nearly 90% of successful recordings, only single reflex responses (not dual) were seen which allowed us to compare pain ratings based on reflex latencies. We found that shorter latency reflexes were just as painful as those in the conventional latency range.

    Conclusion: We found a preponderance of short-latency painful reflex responses. Based on this finding, we suggest that short-latency responses must be considered in future studies. Whether these are signaled by the ultrafast nociceptors remains to be determined.

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  • 3.
    Middleton, Steven J.
    et al.
    Univ Oxford, England.
    Perini, Irene
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Themistocleous, Andreas C.
    Univ Oxford, England; Univ Witwatersrand, South Africa.
    Weir, Greg A.
    Univ Oxford, England; Univ Glasgow, Scotland.
    McCann, Kirsty
    Univ Oxford, England.
    Barry, Allison M.
    Univ Oxford, England.
    Marshall, Andrew
    Univ Liverpool, England.
    Lee, Michael
    Univ Cambridge, England.
    Mayo, Leah M.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Bohic, Manon
    Aix Marseille Univ, France; Rutgers State Univ, NJ 08854 USA.
    Baskozos, Georgios
    Univ Oxford, England.
    Morrison, India
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Loken, Line S.
    Univ Gothenburg, Sweden.
    Mcintyre, Sarah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Staud, Roland
    Univ Florida, FL 32610 USA.
    Sehlstedt, Isac
    Univ Gothenburg, Sweden.
    Johnson, Richard D.
    Univ Gothenburg, Sweden; Univ Florida, FL 32610 USA.
    Wessberg, Johan
    Univ Gothenburg, Sweden.
    Wood, John N.
    UCL, England.
    Woods, Christopher G.
    Univ Cambridge, England.
    Moqrich, Aziz
    Aix Marseille Univ, France.
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bennett, David L.
    Univ Oxford, England.
    Na(v)1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice2022In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 1145, no 10, p. 3637-3653Article in journal (Refereed)
    Abstract [en]

    Middleton, Perini et al. show that the role of Na(v)1.7 extends beyond pain perception. Using a multidisciplinary, cross-species approach, they show that Na(v)1.7 is also essential for C-low threshold mechanoreceptor function in mice and humans, regulating pleasant touch, punctate discrimination and sensitivity to cooling. Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial electromyography (n = 3 CIP participants and n = 8 healthy controls), we found that these patients also have abnormalities in the encoding of affective touch, which is mediated by the specialized afferents C-low threshold mechanoreceptors (C-LTMRs). In the mouse, we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient. Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch.

  • 4.
    Larsson, Max
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Role of C-tactile fibers in pain modulation: animal and human perspectives2022In: Current Opinion in Behavioral Sciences, ISSN 2352-1546, Vol. 43Article in journal (Refereed)
    Abstract [en]

    C-tactile (CT) fibers, a population of unmyelinated (C) fibers that respond particularly well to gentle stroking, are widely believed to subserve affective touch. However, these fibers (termed C low-threshold mechanoreceptors (C-LTMRs) in non-human mammals) have also been proposed to be involved in the modulation of pain. Intriguingly, functional evidence from both human and animal studies indicates that CT/C-LTMR fibers can both contribute to allodynia as well as mediate pain inhibition. In the spinal cord, C-LTMR fibers form glomerular synaptic arrangements, providing input to several populations of interneurons within the nociceptive circuitry. Thus, the CT/C-LTMR system conveys signals that are subject to intricate processing in the spinal cord and is well-situated within spinal sensory pathways to enable the modulation of pain.

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  • 5.
    Mcintyre, Sarah
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Hauser, Steven C.
    Univ Virginia, VA 22903 USA.
    Kusztor, Anikó
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Böhme, Rebecca
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Moungou, Athanasia
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Isager, Peder
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Homman, Lina
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research Division. Linköping University, Department of Culture and Society, Division of Ageing and Social Change. Linköping University, Faculty of Arts and Sciences.
    Novembre, Giovanni
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Israr, Ali
    Facebook, WA USA.
    Lumpkin, Ellen A.
    Columbia Univ, NY 10027 USA.
    Abnousi, Freddy
    Facebook, WA USA.
    Gerling, Gregory J.
    Univ Virginia, VA 22903 USA.
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    The Language of Social Touch Is Intuitive and Quantifiable2022In: Psychological Science, ISSN 0956-7976, E-ISSN 1467-9280, Vol. 33, no 9, p. 1477-1494Article in journal (Refereed)
    Abstract [en]

    Touch is a powerful communication tool, but we have a limited understanding of the role played by particular physical features of interpersonal touch communication. In this study, adults living in Sweden performed a task in which messages (attention, love, happiness, calming, sadness, and gratitude) were conveyed by a sender touching the forearm of a receiver, who interpreted the messages. Two experiments (N = 32, N = 20) showed that within close relationships, receivers could identify the intuitive touch expressions of the senders, and we characterized the physical features of the touches associated with successful communication. Facial expressions measured with electromyography varied by message but were uncorrelated with communication performance. We developed standardized touch expressions and quantified the physical features with 3D hand tracking. In two further experiments (N = 20, N = 16), these standardized expressions were conveyed by trained senders and were readily understood by strangers unacquainted with the senders. Thus, the possibility emerges of a standardized, intuitively understood language of social touch.

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  • 6.
    Mcintyre, Sarah
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    McGlone, Francis
    Liverpool John Moores University, Liverpool, UK.
    Olausson, Håkan
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience.
    The Effects of Ageing on Tactile Function in Humans2021In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Neuroscience, ISSN 0306-4522, Vol. 464, p. 53-58Article, review/survey (Refereed)
    Abstract [en]

    Ageing is accompanied by a steady decline in touch sensitivity and acuity. Conversely, pleasant touch, such as experienced during a caress, is even more pleasant in old age. There are many physiological changes that might explain these perceptual changes, but researchers have not yet identified any specific mechanisms. Here, we review both the perceptual and structural changes to the touch system that are associated with ageing. The structural changes include reduced elasticity of the skin in older people, as well as reduced numbers and altered morphology of skin tactile receptors. Effects of ageing on the peripheral and central nervous systems include demyelination, which affects the timing of neural signals, as well as reduced numbers of peripheral nerve fibres. The ageing brain also undergoes complex changes in blood flow, metabolism, plasticity, neurotransmitter function, and, for touch, the body map in primary somatosensory cortex. Although several studies have attempted to find a direct link between perceptual and structural changes, this has proved surprisingly elusive. We also highlight the need for more evidence regarding age-related changes in peripheral nerve function in the hairy skin, as well as the social and emotional aspects of touch.

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  • 7.
    Rezaei, Merat
    et al.
    Univ Virginia, VA 22903 USA.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Xu, Chang
    Univ Virginia, VA 22903 USA.
    Mcintyre, Sarah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Gerling, Gregory J.
    Univ Virginia, VA 22903 USA.
    Thin Films on the Skin, but not Frictional Agents, Attenuate the Percept of Pleasantness to Brushed Stimuli2021In: 2021 IEEE WORLD HAPTICS CONFERENCE (WHC), IEEE , 2021, p. 49-54Conference paper (Refereed)
    Abstract [en]

    Brushed stimuli are perceived as pleasant when stroked lightly on the skin surface of a touch receiver at certain velocities. While the relationship between brush velocity and pleasantness has been widely replicated, we do not understand how resultant skin movements - e.g., lateral stretch, stick-slip, normal indentation - drive us to form such judgments. In a series of psychophysical experiments, this work modulates skin movements by varying stimulus stiffness and employing various treatments. The stimuli include brushes of three levels of stiffness and an ungloved human finger. The skins friction is modulated via non-hazardous chemicals and washing protocols, and the skins thickness and lateral movement are modulated by thin sheets of adhesive film. The stimuli are hand-brushed at controlled forces and velocities. Human participants report perceived pleasantness per trial using ratio scaling. The results indicate that a brushs stiffness influenced pleasantness more than any skin treatment. Surprisingly, varying the skins friction did not affect pleasantness. However, the application of a thin elastic film modulated pleasantness. Such barriers, though elastic and only 40 microns thick, inhibit the skins tangential movement and disperse normal force. The finding that thin films modulate affective interactions has implications for wearable sensors and actuation devices.

  • 8.
    Böhme, Rebecca
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Veenstra, Helene
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gerdle, Björn
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Anhedonia to Gentle Touch in Fibromyalgia: Normal Sensory Processing but Abnormal Evaluation2020In: Brain Sciences, ISSN 2076-3425, E-ISSN 2076-3425, Vol. 10, no 5, article id 306Article in journal (Refereed)
    Abstract [en]

    Social touch is important for interpersonal interaction. Gentle touch and slow brushing are typically perceived as pleasant, the degree of pleasantness is linked to the activity of the C-tactile (CT) fibers, a class of unmyelinated nerves in the skin. The inability to experience pleasure in general is called anhedonia, a common phenomenon in the chronic pain condition fibromyalgia. Here, we studied the perception and cortical processing of gentle touch in a well-characterized cohort of fibromyalgia. Patients and controls participated in functional brain imaging while receiving tactile stimuli (brushing) on the forearm. They were asked to provide ratings of pleasantness of the tactile stimulus and ongoing pain. We found high distress, pain catastrophizing, and insomnia, and a low perceived state of health in fibromyalgia. Further, patients rated both slow (CT-optimal) and fast (CT-suboptimal) brushing as less pleasant than healthy participants. While there was no difference in brain activity during touch, patients showed deactivation in the right posterior insula (contralateral to the stimulated arm) during pleasantness rating and activation during pain rating. The opposite pattern was observed in healthy participants. Voxel-based morphometry analysis revealed reduced grey matter density in patients, in the bilateral hippocampus and anterior insula. Our results suggest anhedonia to gentle touch in fibromyalgia with intact early-stage sensory processing but dysfunctional evaluative processing. These findings contribute to our understanding of the mechanisms underlying anhedonia in fibromyalgia.

  • 9.
    Ydrefors, Johannes
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Karlsson, Tomas
    University of Gothenburg, Gothenburg, Sweden.
    Wentzel Olausson, Ulrika
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Johansson, Ann-Charlotte
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience.
    Olausson, Håkan
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience.
    Gerdle, Björn
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Automated Nociceptive Withdrawal Reflex Measurements Reveal Normal Reflex Thresholds and Augmented Pain Ratings in Patients with Fibromyalgia2020In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 9, no 6, article id 1992Article in journal (Refereed)
    Abstract [en]

    The nociceptive withdrawal reflex (NWR) is used to probe spinal cord excitability in chronic pain states. Here, we used an automated and unbiased procedure for determining the NWR threshold and compared the reflex thresholds and corresponding pain ratings in a well-characterized cohort of fibromyalgia (n = 29) and matched healthy controls (n = 21). Surface electrical stimuli were delivered to the foot in a stepwise incremental and decremental manner. The surface electromyographic activity was recorded from the ipsilateral tibialis anterior muscle. Fibromyalgia patients reported significantly higher scores for psychological distress and pain-related disability and a significantly lower score for perceived state of health compared to the matched controls. The subjective pain ratings were significantly higher in patients. The NWR thresholds were similar to the controls. In the patients, but not in controls, the NWR thresholds and subjective pain ratings were significantly correlated. Our results showed an increased subjective pain sensitivity in fibromyalgia, but we found no evidence for spinal sensitization based on the reflex measures.

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  • 10.
    Ridderström, Mikael
    et al.
    Gällivare Hospital, Gällivare, Sweden.
    Svantesson, Mats
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Thorell, Oumie
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Western Sydney University, Sydney, Australia.
    Magounakis, Theofilos
    Piteå Älvdals Hospital, Piteå, Sweden.
    Minde, Jan
    Gällivare Hospital, Gällivare, Sweden; Umeå University Hospital, Umeå, Sweden.
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Western Sydney University, Sydney, Australia.
    High prevalence of carpal tunnel syndrome in individuals with rare nerve growth factor-beta mutation2020In: Brain Communications, E-ISSN 2632-1297, Vol. 2, no 2, article id fcaa085Article in journal (Refereed)
    Abstract [en]

    In Sweden, a large family with a point mutation in the nerve growth factor-beta gene has previously been identified. The carriers of this mutation have reduced small-fiber density and selective deficits in deep pain and temperature modalities. The clinical findings in this population are described as hereditary sensory and autonomic neuropathy type V. The purpose of the current study was to investigate the prevalence of carpal tunnel syndrome in hereditary sensory and autonomic neuropathy type V based on clinical examinations and electrophysiological measurements. Further, the cross-sectional area of the median nerve at the carpal tunnel inlet was measured with ultrasonography. Out of 52 known individuals heterozygous for the nerve growth factor-beta mutation in Sweden, 23 participated in the current study (12 males, 11 females; mean age, 55 years; range, 25 to 86 years). All participants answered a health questionnaire and underwent clinical examination followed by median nerve conduction study in a case-control design, and measurement of the nerve cross-sectional area with ultrasonography. The diagnosis of carpal tunnel syndrome was made based on consensus criteria using patient history and nerve conduction study. The prevalence of carpal tunnel syndrome in the hereditary sensory and autonomic neuropathy group was 35% (95% CI 19-55%) or 52% (95% CI 37-74%) depending on whether those individuals who had classic symptoms of carpal tunnel syndrome but negative nerve conduction studies were included or not. Those who had a high likelihood of carpal tunnel syndrome based on classic/probable patient history with positive nerve conduction study had a significantly larger median nerve cross-sectional area than those who had an unlikely patient history with negative nerve conduction study. The prevalence of carpal tunnel syndrome was 10 to 25 times higher in individuals heterozygous for the nerve growth factor-beta mutation than the general Swedish population. Further studies are needed to better understand the underlying pathophysiological mechanisms.

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  • 11.
    Dunn, James S.
    et al.
    Western Sydney Univ, Australia.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Western Sydney Univ, Australia.
    Mahns, David A.
    Western Sydney Univ, Australia.
    Minocycline reduces experimental muscle hyperalgesia induced by repeated nerve growth factor injections in humans: A placebo-controlled double-blind drug-crossover study2020In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 24, no 6, p. 1138-1150Article in journal (Refereed)
    Abstract [en]

    Background Hyperalgesia is a heightened pain response to a noxious stimulus and is a hallmark of many common neuropathic and chronic pain conditions. In a double-blind placebo-controlled drug-crossover trial, the effects of concomitant and delayed minocycline treatment on the initiation and resolution of muscle hyperalgesia were tested. Methods An initial cohort (n = 10) received repeated injections (5 mu g: days 0, 2 and 4) of nerve growth factor (NGF) in the flexor carpi ulnaris muscle of the forearm and pressure pain thresholds were collected at day 0 (control), day 7 (peak) and day 14 (recovery). A second cohort (n = 18) underwent an identical procedure, however, half received a placebo between days 0 and 7 before switching to minocycline from days 7 to 14 (P1/M2), while the remaining subjects received minocycline (day 0: 200mg then 100mg b.i.d. for 7 days) before switching to placebo (M1/P2). Results The initial cohort exhibited a diffuse muscular pain hypersensitivity with a decrease in pressure pain thresholds at day 7 before a partial return to normalcy at day 14. The P1/M2 treatment group exhibited an identical peak in hypersensitivity at day 7, however, after switching to minocycline in week 2 showed a significant reduction in muscle hyperalgesia compared with the initial cohort at day 14. The M1/P2 treatment group had significantly less (similar to 43%) hyperalgesia at day 7 compared with the other groups. Conclusions The study indicates that the administration of minocycline can reduce experimentally induced muscle pain regardless of the time of administration. Significance In a double-blind placebo-controlled drug-crossover study, the common antibiotic minocycline was found to reduce the muscle hyperalgesia induced by intramuscular injection of nerve growth factor. The results of the study showed that both concomitant (pre-emptive) and delayed administration of minocycline can ameliorate the onset and facilitate the resolution of experimentally induced muscle hyperalgesia.

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  • 12.
    Dunn, James S.
    et al.
    School of Medicine, Western Sydney University, Penrith, NSW, Australia.
    Mahns, David A.
    School of Medicine, Western Sydney University, Penrith, NSW, Australia.
    Nagi, Saad S.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience.
    Modulation of Muscle Pain Is Not Somatotopically Restricted: An Experimental Model Using Concurrent Hypertonic-Normal Saline Infusions in Humans2020In: Frontiers in Pain Research, E-ISSN 2673-561X, Vol. 1Article in journal (Refereed)
    Abstract [en]

    We have previously shown that during muscle pain induced by infusion of hypertonic saline (HS), concurrent application of vibration and gentle brushing to overlying and adjacent skin regions increases the overall pain. In the current study, we focused on muscle-muscle interactions and tested whether HS-induced muscle pain can be modulated by innocuous/sub-perceptual stimulation of adjacent, contralateral, and remote muscles. Psychophysical observations were made in 23 healthy participants. HS (5%) was infused into a forearm muscle (flexor carpi ulnaris) to produce a stable baseline pain. In separate experiments, in each of the three test locations (n = 10 per site) - ipsilateral hand (abductor digiti minimi), contralateral forearm (flexor carpi ulnaris), and contralateral leg (tibialis anterior) - 50 μl of 0.9% normal saline (NS) was infused (in triplicate) before, during, and upon cessation of HS-induced muscle pain in the forearm. In the absence of background pain, the infusion of NS was imperceptible to all participants. In the presence of HS-induced pain in the forearm, the concurrent infusion of NS into the ipsilateral hand, contralateral forearm, and contralateral leg increased the overall pain by 16, 12, and 15%, respectively. These effects were significant, reproducible, and time-locked to NS infusions. Further, the NS-evoked increase in pain was almost always ascribed to the forearm where HS was infused with no discernible percept attributed to the sites of NS infusion. Based on these observations, we conclude that intramuscular infusion of HS results in muscle hyperalgesia to sub-perceptual stimulation of muscle afferents in a somatotopically unrestricted manner, indicating the involvement of a central (likely supra-spinal) mechanism.

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  • 13.
    Vickery, Richard M.
    et al.
    UNSW Sydney, Australia; Neurosci Res Australia, Australia.
    Ng, Kevin K. W.
    UNSW Sydney, Australia; Neurosci Res Australia, Australia; UNSW Sydney, Australia; Neurosci Res Australia, Australia.
    Potas, Jason R.
    UNSW Sydney, Australia.
    Shivdasani, Mohit N.
    UNSW Sydney, Australia.
    Mcintyre, Sarah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Birznieks, Ingvars
    UNSW Sydney, Australia; Neurosci Res Australia, Australia.
    Tapping Into the Language of Touch: Using Non-invasive Stimulation to Specify Tactile Afferent Firing Patterns2020In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 14, article id 500Article, review/survey (Refereed)
    Abstract [en]

    The temporal pattern of action potentials can convey rich information in a variety of sensory systems. We describe a new non-invasive technique that enables precise, reliable generation of action potential patterns in tactile peripheral afferent neurons by brief taps on the skin. Using this technique, we demonstrate sophisticated coding of temporal information in the somatosensory system, that shows that perceived vibration frequency is not encoded in peripheral afferents as was expected by either their firing rate or the underlying periodicity of the stimulus. Instead, a burst gap or silent gap between trains of action potentials conveys frequency information. This opens the possibility of new encoding strategies that could be deployed to convey sensory information using mechanical or electrical stimulation in neural prostheses and brain-machine interfaces, and may extend to senses beyond artificial encoding of aspects of touch. We argue that a focus on appropriate use of effective temporal coding offers more prospects for rapid improvement in the function of these interfaces than attempts to scale-up existing devices.

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  • 14.
    Nagi, Saad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Sydney, Australia.
    Marshall, Andrew G.
    Univ Manchester, England; Liverpool John Moores Univ, England.
    Makdani, Adarsh
    Liverpool John Moores Univ, England.
    Jarocka, Ewa
    Umea Univ, Sweden.
    Liljencrantz, Jaquette
    Natl Ctr Complementary and Integrat Hlth, MD 20892 USA; Univ Gothenburg, Sweden.
    Ridderstrom, Mikael
    Umea Univ Hosp, Sweden.
    Shaikh, Sumaiya
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Sydney, Australia.
    ONeill, Francis
    Univ Liverpool, England.
    Saade, Dimah
    NINDS, MD 20892 USA.
    Donkervoort, Sandra
    NINDS, MD 20892 USA.
    Foley, A. Reghan
    NINDS, MD 20892 USA.
    Minde, Jan
    Umea Univ Hosp, Sweden.
    Trulsson, Mats
    Karolinska Inst, Sweden.
    Cole, Jonathan
    Bournemouth Univ, England.
    Bonnemann, Carsten G.
    NINDS, MD 20892 USA.
    Chesler, Alexander T.
    Natl Ctr Complementary and Integrat Hlth, MD 20892 USA.
    Bushnell, M. Catherine
    Natl Ctr Complementary and Integrat Hlth, MD 20892 USA.
    McGlone, Francis
    Liverpool John Moores Univ, England; Univ Liverpool, England.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    An ultrafast system for signaling mechanical pain in human skin2019In: Science Advances, E-ISSN 2375-2548, Vol. 5, no 7, article id eaaw1297Article in journal (Refereed)
    Abstract [en]

    The canonical view is that touch is signaled by fast-conducting, thickly myelinated afferents, whereas pain is signaled by slow-conducting, thinly myelinated ("fast" pain) or unmyelinated ("slow" pain) afferents. While other mammals have thickly myelinated afferents signaling pain (ultrafast nociceptors), these have not been demonstrated in humans. Here, we performed single-unit axonal recordings (microneurography) from cutaneous mechanoreceptive afferents in healthy participants. We identified A-fiber high-threshold mechanoreceptors (A-HTMR5) that were insensitive to gentle touch, encoded noxious skin indentations, and displayed conduction velocities similar to A-fiber low-threshold mechanoreceptors. Intraneural electrical stimulation of single ultrafast A-HTMRs evoked painful percepts. Testing in patients with selective deafferentation revealed impaired pain judgments to graded mechanical stimuli only when thickly myelinated fibers were absent. This function was preserved in patients with a loss-of-function mutation in mechanotransduction channel PIEZO2.These findings demonstrate that human mechanical pain does not require PIEZO2 and can be signaled by fast-conducting, thickly myelinated afferents.

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  • 15.
    Hauser, Steven C.
    et al.
    Univ Virginia, VA 22904 USA.
    Nagi, Saad
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Mcintyre, Sarah
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Israr, Ali
    Facebook Real Labs, WA USA.
    Olausson, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Gerling, Gregory J.
    Univ Virginia, VA 22904 USA.
    From Human-to-Human Touch to Peripheral Nerve Responses2019In: 2019 IEEE WORLD HAPTICS CONFERENCE (WHC), IEEE , 2019, p. 592-597Conference paper (Refereed)
    Abstract [en]

    Human-to-human touch conveys rich, meaningful social and emotional sentiment. At present, however, we understand neither the physical attributes that underlie such touch, nor how the attributes evoke responses in unique types of peripheral afferents. Indeed, nearly all electrophysiological studies use well-controlled but non-ecological stimuli. Here, we develop motion tracking and algorithms to quantify physical attributes indentation depth, shear velocity, contact area, and distance to the cutaneous sensory space (receptive field) of the afferent underlying human-to-human touch. In particular, 2-D video of the scene is combined with 3-D stereo infrared video of the touchers hand to measure contact interactions local to the receptive field of the receivers afferent. The combined and algorithmically corrected measurements improve accuracy, especially of occluded and misidentified fingers. Human subjects experiments track a toucher performing four gestures - single finger tapping, multi-finger tapping, multi-finger stroking and whole hand holding - while action potentials are recorded from a first-order afferent of the receiver. A case study with one rapidly-adapting (Pacinian) and one C-tactile afferent examines temporal ties between gestures and elicited action potentials. The results indicate this method holds promise in determining the roles of unique afferent types in encoding social and emotional touch attributes in their naturalistic delivery.

  • 16.
    Birznieks, Ingvars
    et al.
    UNSW Sydney, Australia; Neurosci Res Australia, Australia; Western Sydney Univ, Australia.
    Mcintyre, Sarah
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Neurosci Res Australia, Australia; Western Sydney Univ, Australia.
    Nilsson, Hanna Maria
    Linköping University. Sweden; Neurosci Res Australia, Australia.
    Nagi, Saad
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Western Sydney Univ, Australia.
    Macefield, Vaughan G.
    Neurosci Res Australia, Australia; Western Sydney Univ, Australia; Baker Heart and Diabet Inst, Australia.
    Mahns, David A.
    Western Sydney Univ, Australia.
    Vickery, Richard M.
    UNSW Sydney, Australia; Neurosci Res Australia, Australia.
    Tactile sensory channels over-ruled by frequency decoding system that utilizes spike pattern regardless of receptor type2019In: eLIFE, E-ISSN 2050-084X, Vol. 8, article id e46510Article in journal (Refereed)
    Abstract [en]

    The established view is that vibrotactile stimuli evoke two qualitatively distinctive cutaneous sensations, flutter (frequencies amp;lt; 60 Hz) and vibratory hum (frequencies amp;gt; 60 Hz), subserved by two distinct receptor types (Meissners and Pacinian corpuscle, respectively), which may engage different neural processing pathways or channels and fulfil quite different biological roles. In psychological and physiological literature, those two systems have been labelled as Pacinian and non-Pacinian channels. However, we present evidence that low-frequency spike trains in Pacinian afferents can readily induce a vibratory percept with the same low frequency attributes as sinusoidal stimuli of the same frequency, thus demonstrating a universal frequency decoding system. We achieved this using brief low-amplitude pulsatile mechanical stimuli to selectively activate Pacinian afferents. This indicates that spiking pattern, regardless of receptor type, determines vibrotactile frequency perception. This mechanism may underlie the constancy of vibrotactile frequency perception across different skin regions innervated by distinct afferent types.

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  • 17.
    Samir Samour, Mohamad
    et al.
    University of Western Sydney, Australia.
    Nagi Saulat, Saad
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. University of Western Sydney, Australia.
    Shortland, Peter John
    Western Sydney University, Australia.
    Mahns, David Anthony
    University of Western Sydney, Australia.
    Minocycline Prevents Muscular Pain Hypersensitivity and Cutaneous Allodynia Produced by Repeated Intramuscular Injections of Hypertonic Saline in Healthy Human Participants2017In: Journal of Pain, ISSN 1526-5900, E-ISSN 1528-8447, Vol. 18, no 8, p. 994-1005Article in journal (Refereed)
    Abstract [en]

    Minocycline, a glial suppressor, prevents behavioral hypersensitivities in animal models of peripheral nerve injury. However, clinical trials of minocycline in human studies have produced mixed results. This study addressed 2 questions: can repeated injections of hypertonic saline (HS) in humans induce persistent hypersensitivity? Can pretreatment with minocycline, a tetracycline antibiotic with microglial inhibitory effects, prevent the onset of hypersensitivity? Twenty-seven healthy participants took part in this double-blind, placebo-controlled study, consisting of 6 test sessions across 2 weeks. At the beginning of every session, pressure-pain thresholds of the anterior muscle compartment of both legs were measured to determine the region distribution and intensity of muscle soreness. To measure changes in thermal sensitivity in the skin overlying the anterior muscle compartment of both legs, quantitative sensory testing was used to measure the cutaneous thermal thresholds (cold sensation, cold pain, warm sensation, and heat pain) and a mild cooling stimulus was applied to assess the presence of cold allodynia. To induce ongoing hypersensitivity, repeated injections of HS were administered into the right tibialis anterior muscle at 48-hour intervals. In the final 2 sessions (days 9 and 14), only sensory assessments were done to plot the recovery after cessation of HS administrations and drug washout. By day 9, nontreated participants experienced a significant bilateral increase in muscle soreness (P amp;lt; .0001), accompanied by the emergence of bilateral cold allodynia in 44% of participants, thus confirming the effectiveness of the model. Placebo-treated participants experienced a bilateral 35% alleviation in muscle soreness (P amp;lt; .0001), with no changes to the prevalence of cold allodynia. In contrast, minocycline-treated participants experienced a bilateral 70% alleviation in muscle soreness (P amp;lt; .0001), additionally, only 10% of minocycline-treated participants showed cold allodynia. This study showed that repeated injections of HS can induce a hypersensitivity that outlasts the acute response, and the development of this hypersensitivity can be reliably attenuated with minocycline pretreatment. Perspective: Four repeated Injections of HS at 48-hour intervals induce a state of persistent hypersensitivity in healthy human participants. This hypersensitivity was characterized by bilateral muscular hyperalgesia and cutaneous cold allodynia, symptoms commonly reported in many chronic pain conditions. Minocycline pretreatment abolished the development of this state. Crown Copyright (C) 2017 Published by Elsevier Inc. on behalf of the American Pain Society

  • 18.
    Liljencrantz, J.
    et al.
    University of Gothenburg, Sweden.
    Strigo, I.
    VA San Francisco Healthcare Syst, CA USA; University of Calif San Francisco, CA 94143 USA.
    Ellingsen, D. M.
    Harvard Medical Sch, MA USA; University of Oslo, Norway.
    Kraemer, H. H.
    Justus Liebig University, Germany.
    Lundblad, L. C.
    University of Gothenburg, Sweden.
    Nagi, Saad
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Western Sydney University, Australia.
    Leknes, S.
    University of Gothenburg, Sweden; University of Oslo, Norway.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. University of Gothenburg, Sweden.
    Slow brushing reduces heat pain in humans2017In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 21, no 7, p. 1173-1185Article in journal (Refereed)
    Abstract [en]

    Background: C-tactile (CT) afferents are unmyelinated low-threshold mechanoreceptors optimized for signalling affective, gentle touch. In three separate psychophysical experiments, we examined the contribution of CT afferents to pain modulation. Methods: In total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub-optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain. Results: Slow brushing was effective in reducing pain, whereas fast brushing or vibration was not. The reduction in pain was significant not only when the CT optimal touch was applied simultaneously with the painful stimulus but also when the two stimuli were separated in time. For subsequent stimulation, the pain reduction was more pronounced for a shorter time interval between brushing and pain. Likewise, the effect was more robust when pain was preceded by a longer duration of brush stimulation. Strong CT-related pain reduction was associated with low anxiety and high calmness scores obtained by a state anxiety questionnaire. Conclusions: Slow brushing - optimal for CT activation - is effective in reducing pain from cutaneous heating. The precise mechanisms for the pain relief are as yet unknown but possible mechanisms include inhibition of nociceptive projection neurons at the level of the dorsal horn as well as analgesia through cortical mechanisms.

  • 19.
    Dunn, James S.
    et al.
    University of Western Sydney, Australia.
    Mahns, David A.
    University of Western Sydney, Australia.
    Nagi, Saad S.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. University of Western Sydney, Australia.
    Why does a cooled object feel heavier? Psychophysical investigations into the Webers Phenomenon2017In: BMC Neuroscience, E-ISSN 1471-2202, Vol. 18, article id 4Article in journal (Refereed)
    Abstract [en]

    Background: It has long been known that a concomitantly cooled stimulus is perceived as heavier than the same object at a neutral temperature-termed Webers Phenomenon (WP). In the current study, we re-examined this phenomenon using well-controlled force and temperature stimuli to explore the complex interplay between thermal and tactile systems, and the peripheral substrates contributing to these interactions. A feedback-controlled apparatus was constructed using a mechanical stimulator attached to a 5- x 5-mm thermode. Force combinations of 0.5 and 1 N (superimposed on 1-N step) were applied to the ulnar territory of dorsal hand. One of the forces had a thermal component, being cooled from 32 to 28 degrees C at a rate of 2 degrees C/s with a 3-s static phase. The other stimulus was thermally neutral (32 degrees C). Participants were asked to report whether the first or the second stimulus was perceived heavier. These observations were obtained in the all-fibre-intact condition and following the preferential block of myelinated fibres by compression of ulnar nerve. Results: In normal condition, when the same forces were applied, all subjects displayed a clear preference for the cooled tactile stimulus as being heavier than the tactile-only stimulus. The frequency of this effect was augmented by an additional similar to 17% when cooling was applied concurrently with the second stimulus. Following compression block, the mean incidence of WP was significantly reduced regardless of whether cooling was applied concurrently with the first or the second stimulus. However, while the effect was abolished in case of former (elicited in amp;lt; 50% of trials), the compression block had little effect in four out of nine participants in case of latter who reported WP in at least 80% of trials (despite abolition of vibration and cold sensations). Conclusions: WP was found to be a robust tactile-thermal interaction in the all-fibre-intact condition. The emergence of inter-individual differences during myelinated block suggests that subjects may adopt strategies, unbeknownst to them, that focus on the dominant input (myelinated fibres, hence WP abolished by block) or the sum of convergent inputs (myelinated and C fibres, hence WP preserved during block) in order to determine differences in perceived heaviness.

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