{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:30:47Z","timestamp":1786696247243,"version":"build-2736575974"},"reference-count":66,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"\n Abstract<\/jats:title>\n \n C\u2010fibre nociceptors display low\u2010level spontaneous firing in the context of tissue injury. Microneurography studies have demonstrated that such low frequency firing can dynamically regulate the activity\u2010dependent slowing (ADS) or temporal pain signal relay of C\u2010fibre nociceptors, thus providing a memory trace of prior activity levels. Here we explore whether low\u2010frequency \u2018manipulation\u2019 can alter C\u2010fibre ADS, in response to subsequent short higher frequency stimulus trains, in compound action potential (CAP) \u2018population\u2019 recordings from isolated rodent dorsal roots of both sexes. In CAP recordings from rat dorsal roots, manipulation (1\u00a0Hz, 2\u00a0min) increased or decreased ADS in response to short stimulus trains (10\u00a0Hz, \u00d740). This dynamic memory was not sex\u2010dependent. The manipulation\u2010induced change in C\u2010fibre ADS correlated with the level of C\u2010fibre ADS pre\u2010manipulation. In CAP recordings from mouse dorsal roots, manipulation (1\u00a0Hz, 1\u00a0min) increased C\u2010fibre ADS in response to short stimulus trains (2\u00a0Hz, \u00d740). This dynamic memory was not sex\u2010dependent, despite a more pronounced ADS in males. The impact of dynamic memory on spinal processing was explored through patch\u2010clamp recording of noxious heat responsive neurons with monosynaptic C\u2010fibre inputs in spinal slices. Manipulation (1\u00a0Hz, 1\u00a0min) increased monosynaptic C\u2010fibre ADS in response to stimulus trains (2\u00a0Hz, \u00d716). This was independent of sex and was associated with synaptic failures. Current\u2010clamp recordings demonstrated that this monosynaptic C\u2010fibre dynamic memory altered action potential firing in noxious heat responsive spinal neurons. In summary, dynamic memory in rodent C\u2010fibres, is not regulated by sex and is communicated to and can alter activity in spinal pain circuits.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Human studies have previously demonstrated that the peripheral nerve C\u2010fibres, which detect potential tissue\u2010damaging stimuli, are able to retain a memory of prior activity levels that influences their subsequent relay of \u2018warning\u2019 signals.<\/jats:p>\n <\/jats:list-item>\n \n This study demonstrates that this \u2018memory\u2019 is also present in rat and mouse tissue damage\u2010detecting peripheral nerve C\u2010fibres and that this memory is not sex\u2010dependent.<\/jats:p>\n <\/jats:list-item>\n \n We demonstrate that this \u2018memory\u2019 is evident in the C\u2010fibres that directly activate spinal cord neurons responsive to potential tissue damaging heat stimuli and can dynamically regulate their activity.<\/jats:p>\n <\/jats:list-item>\n \n This suggests that ongoing firing of these tissue damage\u2010detecting C\u2010fibres in the context of injury can dynamically regulate how the spinal cord processes pain.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp290239","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:10:06Z","timestamp":1786695006000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic memory in rodent C\u2010fibres and its impact on spinal nociceptive processing"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6941-1188","authenticated-orcid":false,"given":"Atanaska N.","family":"Velichkova","sequence":"first","affiliation":[{"name":"Institute for Neuroscience and Cardiovascular Research University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-3364","authenticated-orcid":false,"given":"Carole","family":"Torsney","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience and Cardiovascular Research University of Edinburgh Edinburgh UK"},{"name":"Simons Initiative for the Developing Brain University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"issue":"3","key":"e_1_2_5_2_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0014-2999(94)90483-9","article-title":"Effects of opioids and non\u2010opioids on c\u2010fos\u2010like immunoreactivity induced in rat lumbar spinal cord neurons by noxious heat stimulation","volume":"258","author":"Abbadie C.","year":"1994","journal-title":"European Journal of Pharmacology"},{"issue":"7","key":"e_1_2_5_3_1","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1113\/jphysiol.2011.224436","article-title":"Sodium channel slow inactivation and adaptation in C\u2010fibres","volume":"590","author":"Baker M. 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