BRIEF RESEARCH REPORT article
Front. Pain Res.
Sec. Pain Mechanisms
Volume 6 - 2025 | doi: 10.3389/fpain.2025.1648374
Fear-learning is altered in a mouse neuropathic pain model
Provisionally accepted
Neda Assareh
Eddy E SokolajSaima Sadia
Kristen E AndersonCaitlin FrithOlivia B WallsVanessa A Mitchell
Christopher W Vaughan
Bryony Laura Winters*- The University of Sydney, Sydney, Australia
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Background: While chronic neuropathic pain is characterised by abnormal pain signs, such as allodynia, highly disabling co-morbidities, such as anxiety and depression, have a major impact. It is thought that these co-morbidities arise from learning maladaptations related to inappropriate associations between pain and stimulus/environmental cues. However, the impact of animal neuropathic pain models on the interactions between fear-learning, pain and anxiety are poorly understood, particularly during early stages prior to establishment of anxiety.We examined the impact of fear-conditioning on fear, anxiety-like behaviours and cold/mechanical allodynia in the mouse sciatic nerve chronic constriction injury (CCI) model of neuropathic pain, at an early post-injury time point.Results: At two weeks post-surgery, CCI and sham operated mice displayed similar acquisition of fear-like freezing responses to a paired audio-tone/footshock fear-conditioning paradigm. On the following day, CCI mice displayed greater freezing than sham mice in response to the same context and subsequent tone presentations. While CCI and sham mice display similar anxiety-like behaviour in the light-dark box and open field, these were increased by fear-conditioning in CCI but not mice. Finally, CCI but not sham surgery produced cold and mechanical allodynia, however, these were unaffected by fear-conditioning.These findings indicate that a neuropathic pain model enhances learned context/cue evoked fear behaviours at an early stage following nerve-injury. Furthermore, fear-conditioning enhances anxiety-like behaviour, before such behaviour is normally developed. Thus, fearconditioning induces exaggerated fear-learning which triggers enhanced fear and anxiety, even during early stages of chronic neuropathic pain.
Keywords: neuropathic pain, Fear, Fear conditioning, fear learning, Freezing, Anxiety, allodynia
Received: 17 Jun 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Assareh, Sokolaj, Sadia, Anderson, Frith, Walls, Mitchell, Vaughan and Winters. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bryony Laura Winters, The University of Sydney, Sydney, Australia
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