{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:02:25Z","timestamp":1792674145891,"version":"4.5.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1158"],"award-info":[{"award-number":["SFB 1158"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroscience"],"published-print":{"date-parts":[[2018,9]]},"DOI":"10.1016\/j.neuroscience.2018.03.006","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T19:52:16Z","timestamp":1521143536000},"page":"4-12","source":"Crossref","is-referenced-by-count":30,"special_numbering":"C","title":["Low-Frequency Stimulation of Silent Nociceptors Induces Secondary Mechanical Hyperalgesia in Human Skin"],"prefix":"10.1016","volume":"387","author":[{"given":"Katja","family":"Sauerstein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Liebelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Namer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Rukwied","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schmelz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuroscience.2018.03.006_b0005","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/j.pain.0000000000000753","article-title":"Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles","volume":"158","author":"Baron","year":"2017","journal-title":"Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0010","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0304-3959(93)90207-6","article-title":"Development of secondary hyperalgesia following nonpainful thermal stimulation of the skin a psychophysical study in man","volume":"54","author":"Cervero","year":"1993","journal-title":"Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0015","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1213\/01.ANE.0000132995.35119.99","article-title":"The effect of intravenous infusion of adenosine on electrically evoked hyperalgesia in a healthy volunteer model of central sensitization","volume":"99","author":"Chizh","year":"2004","journal-title":"Anesth Analg"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0020","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.1523\/JNEUROSCI.2061-14.2015","article-title":"Selective activation of microglia facilitates synaptic strength","volume":"35","author":"Clark","year":"2015","journal-title":"J Neurosci"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0025","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1093\/bja\/aen088","article-title":"Spinal cord mechanisms of pain","volume":"101","author":"D'Mello","year":"2008","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0030","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1744-8069-4-18","article-title":"Long-term potentiation at C-fibre synapses by low-level presynaptic activity in vivo","volume":"4","author":"Drdla","year":"2008","journal-title":"Mol Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0035","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1097\/WNR.0b013e3281e72cff","article-title":"Rapid flare development evoked by current frequency-dependent stimulation analyzed by full-field laser perfusion imaging","volume":"18","author":"Dusch","year":"2007","journal-title":"NeuroReport"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0040","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.sjpain.2010.08.002","article-title":"Cross-over evaluation of electrically induced pain and hyperalgesia","volume":"1","author":"Dusch","year":"2010","journal-title":"Scand J Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0045","doi-asserted-by":"crossref","first-page":"e1600990","DOI":"10.1126\/sciadv.1600990","article-title":"In vivo characterization of distinct modality-specific subsets of somatosensory neurons using GCaMP","volume":"2","author":"Emery","year":"2016","journal-title":"Sci Adv"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0050","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1097\/j.pain.0000000000000492","article-title":"Neuropathic pain: an updated grading system for research and clinical practice","volume":"157","author":"Finnerup","year":"2016","journal-title":"Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0055","doi-asserted-by":"crossref","DOI":"10.1093\/brain\/awv108","article-title":"Capsaicin-sensitive C- and A-fibre nociceptors control long-term potentiation-like pain amplification in humans","author":"Henrich","year":"2015","journal-title":"Brain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0060","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1126\/science.1127233","article-title":"Synaptic amplifier of inflammatory pain in the spinal dorsal horn","volume":"312","author":"Ikeda","year":"2006","journal-title":"Science"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0065","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.jpain.2012.09.008","article-title":"Differential effects of low dose lidocaine on C-fiber classes in humans","volume":"13","author":"Kankel","year":"2012","journal-title":"J Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0070","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1016\/j.pain.2012.05.017","article-title":"High spontaneous activity of C-nociceptors in painful polyneuropathy","volume":"153","author":"Kleggetveit","year":"2012","journal-title":"Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0075","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1523\/JNEUROSCI.1222-03.2004","article-title":"Perceptual correlates of nociceptive long-term potentiation and long-term depression in humans","volume":"24","author":"Klein","year":"2004","journal-title":"J Neurosci"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0080","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1093\/brain\/117.3.579","article-title":"Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain","volume":"117","author":"Koltzenburg","year":"1994","journal-title":"Brain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0085","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1097\/00000542-200108000-00022","article-title":"A new model of electrically evoked pain and hyperalgesia in human skin: the effects of intravenous alfentanil, S(+)-ketamine, and lidocaine","volume":"95","author":"Koppert","year":"2001","journal-title":"Anesthesiology"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0090","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1126\/science.aah5715","article-title":"Gliogenic LTP spreads widely in nociceptive pathways","volume":"354","author":"Kronschlager","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0095","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1152\/jn.1991.66.1.190","article-title":"Neurogenic hyperalgesia psychophysical studies of underlying mechanisms","volume":"66","author":"LaMotte","year":"1991","journal-title":"JNeurophysiol"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0100","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/papr.12339","article-title":"Effects of current density on nociceptor activation upon electrical stimulation in humans","volume":"16","author":"Landmann","year":"2016","journal-title":"Pain Practice"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0105","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.jpain.2009.06.012","article-title":"Central sensitization: a generator of pain hypersensitivity by central neural plasticity","volume":"10","author":"Latremoliere","year":"2009","journal-title":"J Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0110","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1152\/jn.1997.78.4.1973","article-title":"Characterization of long-term potentiation of C-fiber-evoked potentials in spinal dorsal horn of adult rat: essential role of NK1 and NK2 receptors","volume":"78","author":"Liu","year":"1997","journal-title":"J Neurophysiol"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0115","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1093\/bja\/71.2.201","article-title":"Time course of primary and secondary hyperalgesia after heat injury to the skin","volume":"71","author":"Moiniche","year":"1993","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0120","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/j.pain.2011.02.005","article-title":"Inhibition of hyperalgesia by conditioning electrical stimulation in a human pain model","volume":"152","author":"Nickel","year":"2011","journal-title":"Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0125","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/ana.410330509","article-title":"Mechanical hyperalgesias in neuropathic pain patients: dynamic and static subtypes","volume":"33","author":"Ochoa","year":"1993","journal-title":"Ann Neurol"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0130","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1152\/jn.1999.82.3.1164","article-title":"Electrophysiological assessment of the cutaneous arborization of Adelta-fiber nociceptors","volume":"82","author":"Peng","year":"1999","journal-title":"J Neurophysiol"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0135","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1097\/00001756-199905140-00022","article-title":"A new human experimental pain model: the heat\/capsaicin sensitization model","volume":"10","author":"Petersen","year":"1999","journal-title":"NeuroReport"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0140","doi-asserted-by":"crossref","first-page":"e103556","DOI":"10.1371\/journal.pone.0103556","article-title":"Differential axonal conduction patterns of mechano-sensitive and mechano-insensitive nociceptors\u2013a combined experimental and modelling study","volume":"9","author":"Petersson","year":"2014","journal-title":"PLoS ONE"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0145","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.neuroscience.2017.11.047","article-title":"Human vs. mouse nociceptors \u2013 similarities and differences","volume":"387","author":"Rostock","year":"2018","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0150","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1744-8069-3-9","article-title":"Understanding LTP in pain pathways","volume":"3","author":"Sandkuhler","year":"2007","journal-title":"Mol Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0155","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1097\/00001756-200002280-00041","article-title":"Which nerve fibers mediate the axon reflex flare in human skin?","volume":"11","author":"Schmelz","year":"2000","journal-title":"NeuroReport"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0160","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/brain\/123.3.560","article-title":"Encoding of burning pain from capsaicin-treated human skin in two categories of unmyelinated nerve fibres","volume":"123","author":"Schmelz","year":"2000","journal-title":"Brain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0165","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1523\/JNEUROSCI.15-01-00333.1995","article-title":"Novel classes of responsive and unresponsive C nociceptors in human skin","volume":"15","author":"Schmidt","year":"1995","journal-title":"J Neurosci"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0170","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1152\/jn.2002.88.4.1859","article-title":"Innervation territories of mechano-insensitive C nociceptors in human skin","volume":"88","author":"Schmidt","year":"2002","journal-title":"J Neurophysiol"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0175","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.pain.2011.08.015","article-title":"Microneurographic identification of spontaneous activity in C-nociceptors in neuropathic pain states in humans and rats","volume":"153","author":"Serra","year":"2012","journal-title":"Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0180","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/ana.24065","article-title":"Hyperexcitable C nociceptors in fibromyalgia","volume":"75","author":"Serra","year":"2014","journal-title":"Ann Neurol"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0185","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0304-3959(89)90079-1","article-title":"Dose-dependent pain and mechanical hyperalgesia in humans after intradermal injection of capsaicin","volume":"38","author":"Simone","year":"1989","journal-title":"Pain"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0190","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.bpj.2014.12.034","article-title":"C-fiber recovery cycle supernormality depends on ion concentration and ion channel permeability","volume":"108","author":"Tigerholm","year":"2015","journal-title":"Biophys J"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0195","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/j.1748-1716.1974.tb05755.x","article-title":"Afferent C units responding to mechanical, thermal and chemical stimuli in human non-glabrous skin","volume":"92","author":"Torebj\u00f6rk","year":"1974","journal-title":"Acta Physiol Scand"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0200","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1136\/jnnp.37.6.653","article-title":"Responses in human A and C fibres to repeated electrical intradermal stimulation","volume":"37","author":"Torebj\u00f6rk","year":"1974","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0205","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1113\/jphysiol.1992.sp019069","article-title":"Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans","volume":"448","author":"Torebj\u00f6rk","year":"1992","journal-title":"J Physiol (Lond)"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0210","doi-asserted-by":"crossref","first-page":"10184","DOI":"10.1523\/JNEUROSCI.19-22-10184.1999","article-title":"Functional attributes discriminating mechano-insensitive and mechano-responsive C nociceptors in human skin","volume":"19","author":"Weidner","year":"1999","journal-title":"J Neurosci"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0215","doi-asserted-by":"crossref","first-page":"6704","DOI":"10.1523\/JNEUROSCI.22-15-06704.2002","article-title":"Neural signal processing: the underestimated contribution of peripheral human C-fibers","volume":"22","author":"Weidner","year":"2002","journal-title":"J Neurosci"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0220","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/0014-2999(90)90293-F","article-title":"Diffuse noxious inhibitory controls in man: involvement of an opioidergic link","volume":"182","author":"Willer","year":"1990","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0225","doi-asserted-by":"crossref","first-page":"4122","DOI":"10.1038\/ncomms5122","article-title":"Three functionally distinct classes of C-fibre nociceptors in primates","volume":"5","author":"Wooten","year":"2014","journal-title":"Nat Commun"},{"issue":"RC137","key":"10.1016\/j.neuroscience.2018.03.006_b0230","first-page":"131","article-title":"Early onset of spontaneous activity in uninjured C-fiber nociceptors after injury to neighboring nerve fibers","volume":"21","author":"Wu","year":"2001","journal-title":"J Neurosci"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0235","doi-asserted-by":"crossref","first-page":"7746","DOI":"10.1523\/JNEUROSCI.22-17-07746.2002","article-title":"Degeneration of myelinated efferent fibers induces spontaneous activity in uninjured C-fiber afferents","volume":"22","author":"Wu","year":"2002","journal-title":"J Neurosci"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0240","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1007\/s00221-016-4653-1","article-title":"Exploration of the conditioning electrical stimulation frequencies for induction of long-term potentiation-like pain amplification in humans","volume":"234","author":"Xia","year":"2016","journal-title":"Exp Brain Res"},{"key":"10.1016\/j.neuroscience.2018.03.006_b0245","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.23235","article-title":"Voltage-gated Na+ currents in human dorsal root ganglion neurons","volume":"6","author":"Zhang","year":"2017","journal-title":"Elife"}],"container-title":["Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S030645221830188X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S030645221830188X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T20:06:22Z","timestamp":1538597182000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S030645221830188X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9]]},"references-count":49,"alternative-id":["S030645221830188X"],"URL":"https:\/\/doi.org\/10.1016\/j.neuroscience.2018.03.006","relation":{},"ISSN":["0306-4522"],"issn-type":[{"value":"0306-4522","type":"print"}],"subject":[],"published":{"date-parts":[[2018,9]]}}}