{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:03:35Z","timestamp":1789506215803,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004497","name":"Onderzoeksraad, KU Leuven","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004497","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      In humans transcutaneous high\u2010frequency electrical stimulation (HFS) has been reported to increase pain elicited by single electrical stimuli at the HFS\u2010treated site, an effect thought to represent the perceptual correlate of homosynaptic long\u2010term potentiation (LTP) at spinal C fibre synapses. However this finding has not been consistently replicated. In previous studies hyperalgesia has been commonly assessed using rectangular electrical pulses, which may not sufficiently activate C fibre nociceptors. In two preregistered experiments we investigated whether 4 Hz sinusoidal electrical stimulation, which has been shown to reliably activate C fibres, elicits homotopic hyperalgesia after HFS in healthy human volunteers. In both experiments transcutaneous HFS was applied to one of the two forearms, resulting in enhanced pinprick sensitivity in the adjacent skin. In experiment 1 (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a026) participants received 60\u00a0s of 4 Hz sinusoidal stimulation at 0.2\u00a0mA before HFS and at 10, 30 and 50\u00a0min afterwards on each arm. The repeated\u2010measures ANOVA on the pain ratings before HFS and at 50\u00a0min after HFS revealed no significant interaction between time and arm. To address the possibility that the 4 Hz stimulation given before HFS may have prevented the induction of hyperalgesia, and to enhance C fibre recruitment, a second experiment was conducted (experiment 2,\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a028). Participants received 60\u00a0s of 4 Hz sinusoidal stimulation at 0.7\u00a0mA, 50 min after HFS on each arm. The Bayesian paired\n                      <jats:italic>t<\/jats:italic>\n                      test provided moderate evidence against a difference in pain ratings between the two arms. Taken together we found no evidence for homotopic hyperalgesia to C fibre stimulation after HFS.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70824-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>High\u2010frequency electrical stimulation (HFS) of peripheral nociceptors produces homosynaptic long\u2010term potentiation (LTP) at spinal C fibre synapses in animals.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>4 Hz sinusoidal electrical stimulation preferentially activates C fibres.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We found no evidence for hyperalgesia to the 4 Hz stimulation after HFS in humans.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp290487","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:38:55Z","timestamp":1788759535000},"page":"7911-7923","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["No evidence for homotopic hyperalgesia to C fibre stimulation after transcutaneous high\u2010frequency stimulation in humans"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7299-0750","authenticated-orcid":false,"given":"Enrique","family":"Velasco","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine KU Leuven  Leuven Belgium"},{"name":"Neuroscience in Physiotherapy Independent Research Group  Elche Spain"},{"name":"Pain Focus Group, Leuven Brain Institute KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2541-5126","authenticated-orcid":false,"given":"Eleonora","family":"Ricci","sequence":"additional","affiliation":[{"name":"Faculty of Psychology and Educational Sciences, Research Group Health Psychology KU Leuven  Leuven Belgium"},{"name":"Department of Psychology University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noortje","family":"Verhaegen","sequence":"additional","affiliation":[{"name":"Faculty of Psychology and Educational Sciences, Research Group Health Psychology KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M.","family":"Torta","sequence":"additional","affiliation":[{"name":"Pain Focus Group, Leuven Brain Institute KU Leuven  Leuven Belgium"},{"name":"Faculty of Psychology and Educational Sciences, Research Group Health Psychology KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6668-3217","authenticated-orcid":false,"given":"Emanuel N.","family":"van den Broeke","sequence":"additional","affiliation":[{"name":"Pain Focus Group, Leuven Brain Institute KU Leuven  Leuven Belgium"},{"name":"Faculty of Psychology and Educational Sciences, Research Group Health Psychology KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2003.08.007"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpain.2025.1556429"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000003093"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv108"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080659"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1127233"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2025.111571"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25231"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1222-03.2004"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2006.09.008"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.06.001"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah5715"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00130.2025"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.10.045"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000003605"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000003166"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1997.6688"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103556"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001912"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv193"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1998.00278.x"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2023.01.009"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199711100-00002"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6241-10.2011"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001841"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00274.2019"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272599"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00651.2013"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00289.2021"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.200830"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-22-10184.1999"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP280269"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-016-4653-1"}],"container-title":["The 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