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  • 1.
    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.

  • 2.
    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 (Online), ISSN 1471-2202, 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.

  • 3.
    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.

  • 4.
    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.

  • 5.
    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

1 - 5 of 5
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