Repeated exposure of naïve and peripheral nerve-injured mice to a snake as an experimental model of post-traumatic stress disorder and its co-morbidity with neuropathic pain.

Abstract Confrontation of rodents by natural predators provides a number of advantages as a model for traumatic or stressful experience. Using this approach, one of the aims of this study was to investigate a model for the study of post-traumatic stress disorder (PTSD)-related behaviour in mice. Moreover, because PTSD can facilitate the establishment of chronic pain (CP), and in the same way, patients with CP have an increased tendency to develop PTSD when exposed to a traumatic event, our second aim was to analyse whether this comorbidity can be verified in the new paradigm. C57BL/6 male mice underwent chronic constriction injury of the sciatic nerve (CCI), a model of neuropathic CP, or not (sham groups) and were submitted to different threatening situations. Threatened mice exhibited enhanced defensive behaviours, as well as significantly enhanced risk assessment and escape behaviours during context reexposure. Previous snake exposure reduced open-arm time in the elevated plus-maze test, suggesting an increase in anxiety levels. Sham mice showed fear-induced antinociception immediately after a second exposure to the snake, but 1 week later, they exhibited allodynia, suggesting that multiple exposures to the snake led to increased nociceptive responses. Moreover, after reexposure to the aversive environment, allodynia was maintained. CCI alone produced intense allodynia, which was unaltered by exposure to either the snake stimuli or reexposure to the experimental context. Together, these results specifically parallel the behavioural symptoms of PTSD, suggesting that the snake/exuvia/reexposure procedure may constitute a useful animal model to study PTSD.