Fear-learning is altered in a mouse neuropathic pain model

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.

At 2 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, fear-conditioning induces exaggerated fear-learning which triggers enhanced fear and anxiety, even during early stages of chronic neuropathic pain.