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  • 1.
    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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