Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction

Jeffrey S. Mogil, Robert E. Sorge, Michael L. Lacroix-Fralish, Shad B. Smith, Anny Fortin, Susana G. Sotocinal, Jennifer Ritchie, Jean Sebastien Austin, Ara Schorscher-Petcu, Kara Melmed, Jan Czerminski, Rosalie A. Bittong, J. Brad Mokris, John K. Neubert, Claudia M. Campbell, Robert R. Edwards, James N. Campbell, Jacqueline N. Crawley, William R. Lariviere, Margaret R. WallaceWendy F. Sternberg, Carey D. Balaban, Inna Belfer, Roger B. Fillingim

Research output: Contribution to journalArticle

Abstract

Quantitative trait locus mapping of chemical/inflammatory pain in the mouse identified the Avpr1a gene, which encodes the vasopressin-1A receptor (V1AR), as being responsible for strain-dependent pain sensitivity to formalin and capsaicin. A genetic association study in humans revealed the influence of a single nucleotide polymorphism (rs10877969) in AVPR1A on capsaicin pain levels, but only in male subjects reporting stress at the time of testing. The analgesic efficacy of the vasopressin analog desmopressin revealed a similar interaction between the drug and acute stress, as desmopressin inhibition of capsaicin pain was only observed in nonstressed subjects. Additional experiments in mice confirmed the male-specific interaction of V1AR and stress, leading to the conclusion that vasopressin activates endogenous analgesia mechanisms unless they have already been activated by stress. These findings represent, to the best of our knowledge, the first explicit demonstration of analgesic efficacy depending on the emotional state of the recipient, and illustrate the heuristic power of a bench-to-bedside-to-bench translational strategy.

Original languageEnglish (US)
Pages (from-to)1569-1573
Number of pages5
JournalNature neuroscience
Volume14
Issue number12
DOIs
StatePublished - Dec 1 2011

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mogil, J. S., Sorge, R. E., Lacroix-Fralish, M. L., Smith, S. B., Fortin, A., Sotocinal, S. G., Ritchie, J., Austin, J. S., Schorscher-Petcu, A., Melmed, K., Czerminski, J., Bittong, R. A., Mokris, J. B., Neubert, J. K., Campbell, C. M., Edwards, R. R., Campbell, J. N., Crawley, J. N., Lariviere, W. R., ... Fillingim, R. B. (2011). Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction. Nature neuroscience, 14(12), 1569-1573. https://doi.org/10.1038/nn.2941