Background

Chronic neuropathic pain is a debilitating condition that deeply affects quality of life and is a major socioeconomic burden. The anticipation of pain can be a major source of fear and anxiety for chronic pain sufferers, leading to or compounding stress and anxiety related disorders. However, the underlying mechanisms and relationship between pain and fear are poorly understood. We addressed this by using an animal model of neuropathic pain to examine fear-like and analgesic responses in a fear-conditioning conditioning protocol.

Methods

Neuropathic pain was modelled by chronic constriction injury (CCI) of the sciatic in male C57BL/6 mice. These were compared to control surgery (sham) and no surgery (naïve) mice. At 14-days post-surgery, mice then underwent a fear conditioning protocol to assess fear learning behaviour by associating an innocuous audio tone with an electrical footshock. On the following days, mice underwent assessment of their fear-like freezing or analgesic responses (Hargreaves tester) to the audio tone alone in a different environmental context.

Findings

On the day following fear-conditioning, naïve mice expressed not only fear-like freezing behaviour, but also an analgesic response to the cue conditioned stimulus. Compare to control sham mice, CCI mice displayed disrupted analgesic and freezing responses to the cue conditioned stimulus.

Conclusion

As observed previously for fear-behaviour, the present study demonstrates that an analgesic response can be evoked by a non-contextual cue in a fear-learning paradigm in mice. This co-ordinated fear-analgesic response is disrupted in a chronic neuropathic pain model.