Experimental Neuropathy in Mice Is Associated with Delayed Behavioral Changes Related to Anxiety and Depression

Abstract

Nerve injury can trigger affective disturbances in mice that appear much later than sensory hypersensitivity.

Validation of an air-puff passive-avoidance paradigm for assessment of aversive learning and memory in rat models of chronic pain

“…Our results suggest that aversive learning and memory assessed in our air-puff passive-avoidance paradigm were not affected in either the inflammatory (CFA) or neuropathic (SNL) pain models under the conditions and at the time-point described. This result supports the findings of Suzuki et al (2007) and other related research which has shown that learned helplessness in the forcedswim test and active avoidance in the place-escape/avoidance paradigm can be acquired in rat models of chronic pain (Goncalves et al, 2008;Hu et al, 2009;Leite-Almeida et al, 2009;Suzuki et al, 2007). These findings relating to aversive learning and memory are somewhat surprising given the evidence, discussed above, that chronic pain is associated with impairment in other cognitive domains, both clinically and preclinically.…”

“…Although aversive learning and memory were not investigated by Leite-Almeida and colleagues, it is possible that pain-related deficits in these may also be detectable in mid-aged rats, despite failure to detect any deficits in the young adult rats (6-9 weeks old on arrival) used in the present study. However, it is also possible, given the results of the present study and the findings of Suzuki et al (2007), that aversive memory is simply unaffected in rodent models of chronic pain, or that passive-avoidance responding is not a reliable predictor of pain-related cognitiveimpairment. The learning and memory mechanisms affected by chronic pain may be distinct from those affected by scopolamine, and thus more specific behavioural paradigms may be required to detect cognitive deficits associated with chronic pain.…”

“…In these studies increased pain responding was associated with a preference for a "high-risk" lever associated with larger but more infrequent rewards than the To our knowledge, only one published study has investigated passive avoidance aversive learning and memory in an animal model of chronic pain. Suzuki et al (2007) tested performance in a foot-shock-induced passive-avoidance paradigm in nerve-injured mice. The paradigm used a step-through light/dark arena and the aversive stimulus consisted of a 0.2 mA electric shock.…”

“…Therefore, although we observed robust, consistent expression of chronic pain-like behaviours at the post-surgery time-point selected for passive-avoidance testing, it is possible that cognitive impairment, as assessed using this paradigm, may not have developed by this time-point. However, the time-point selected in the present study (days 18-20 post-SNL or post-CFA) was based on previous studies that have demonstrated pain-related alterations in both emotional (Suzuki et al, 2007) and cognitive (Pais-Vieira et al, 2009a) behaviours within a similar timeframe relative to injury. A recent study by Leite-Almeida et al (2009) has indicated that age is another important factor in expression of pain-related cognitive impairment, with mid-aged (9 month-old) rats, but not young (3 month-old) or old (22 month-old) rats, showing an increased susceptibility to impaired performance in a Morris Water maze reversal task.…”

“…However, such paradigms do not typically include a retention trial to measure recall of the learned response. Spinal nerve ligation, a model of chronic neuropathic pain, did not affect aversive learning and memory in a foot-shock-induced passive-avoidance paradigm in mice (Suzuki et al, 2007). Passive avoidance, a fear-motivated classical conditioning paradigm, is used to measure aversive learning and memory in rodents.…”