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Male-specific conditioned pain hypersensitivity in mice and humans

Martin, L. J., Acland, E. L., Cho, C., Gandhi, W., Chen, D., Corley, E., Kadoura, B., Levy, T., Mirali, S., Tohyama, S., Khan, S., MacIntyre, L. C., Carlson, E. N., Schweinhardt, P. and Mogil, J. S. (2019) Male-specific conditioned pain hypersensitivity in mice and humans. Current Biology, 29 (2). 192-201.e4. ISSN 0960-9822

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To link to this item DOI: 10.1016/j.cub.2018.11.030

Abstract/Summary

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.

Item Type:Article
Refereed:Yes
Divisions:Interdisciplinary centres and themes > Centre for Integrative Neuroscience and Neurodynamics (CINN)
ID Code:88789
Publisher:Elsevier
Publisher Statement:The study was conceived by L.J.M. and J.S.M. Experiments were designed by L.J.M., P.S., and J.S.M. Experiments were performed by L.J.M., E.L.A., C.C., W.G., D.C., E.C., B.K., T.L., S.M., S.T., and L.C.M. The paper was written by L.J.M. and J.S.M. and edited by E.L.A., W.G., E.N.C., and P.S.

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