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Behavioral measures of persistent pain in mice

  • Author(s): Urban, Rochelle
  • Advisor(s): Basbaum, Allan I
  • et al.
Abstract

The use of animal models in the understanding of the neurobiology of pain perception is essential for the development of new pharmacotherapies. Yet, in modeling human clinical experience, there is a lack of meaningful and appropriate dependent variables of pain-related behaviors in the mouse. In this thesis, we address the problem of finding behavioral measures of pain in mice that fully encompass the range of experience inherent to human pain conditions. Therefore, in this work complex behaviors were assessed as potential measures of persistent pain in mice

We investigated a wide range of quality of life behaviors in three classic pain models: spared nerve injury, chronic constriction injury and injection of complete Freund's adjuvant. Mechanical hypersensitivity is prominent in each of these conditions and persists for many weeks. To assess more complex behavioral outcomes, home cage behavior was continuously monitored after injury and a battery of motor disability and affective behavior tests were performed on these mice. No model of chronic pain produced long-lasting changes to behaviors of daily life, either in the home cage or in tests of affect and disability.

Next, we observed behaviors in three other models of persistent pain: osteoarthritis, disc-degeneration, and dental pulp exposure. In a pilot study of the former two models, mice with joint degeneration were tested for locomotor ability and motivation, but showed no signs of disability. Lastly, we measured behavior in the setting of dental pulp inflammation, for which there is no standard method of measuring pain levels. As with other models, pulpal injury also did not impact behavior in the home cage. Instead, we used an operant assay of sucrose consumption as a measure of dental pain in mice. Data from this task suggest that pain can, in fact, influence some elements of complex behavior. However, as alteration in daily life activities is the feature that is so disrupted in patients with chronic pain, our results suggest that many murine pain models do not fully reflect the human conditions and raise questions regarding the limitations of these models in pain research.

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