The Effect of Peripheral Nerve-injury on Depression and Anxiety-like Behaviours in Mice

Past animal studies examining the relationship between depression and chronic pain have used only male rodents and often only assessed behaviours 7 to 14 days after an injury. To determine whether chronic pain results in a sexually dimorphic presentation of depression-like behaviours, I conducted a series of experiments assessing male and female mice at 14, 28, and 42 days after a peripheral nerve injury. I found that mice did not show any changes in behaviours 14 or 28 days. At 42 days post-surgery male mice with a nerve injury showed significantly more depressive-like behaviours than the sham group, however females did not. This suggest that results from male rodents may not be generalizable to females and that studies assessing mental health and chronic pain in rodents should assess behaviour over longer periods of time as to be more representative of long-term pain experiences.M.A

Male-specific conditioned pain hypersensitivity in mice and humans

Pain memories are hypothesized to be critically involved in the transition of pain from an acute to a chronic state. To help elucidate the underlying neurobiological mechanisms of pain memory, we developed novel paradigms to study context-dependent pain hypersensitivity in mouse and human subjects, respectively. We find that both mice and people become hypersensitive to acute, thermal nociception when tested in an environment previously associated with an aversive tonic pain experience. This sensitization persisted for at least 24 hr and was only present in males of both species. In mice, context-dependent pain hypersensitivity was abolished by castrating male mice, pharmacological blockade of the hypothalamic-pituitary-adrenal axis, or intracerebral or intrathecal injections of zeta inhibitory peptide (ZIP) known to block atypical protein kinase C (including the protein kinase Mz isoform). In humans, men, but not women, self-reported higher levels of stress when tested in a room previously associated with tonic pain. These models provide a new, completely translatable means for studying the relationship between memory, pain, and stress