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

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.

SUBMITTER: Mogil JS

PROVIDER: S-EPMC3225498 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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

Mogil Jeffrey S JS Sorge Robert E RE LaCroix-Fralish Michael L ML Smith Shad B SB Fortin Anny A Sotocinal Susana G SG Ritchie Jennifer J Austin Jean-Sebastien JS Schorscher-Petcu Ara A Melmed Kara K Czerminski Jan J Bittong Rosalie A RA Mokris J Brad JB Neubert John K JK Campbell Claudia M CM Edwards Robert R RR Campbell James N JN Crawley Jacqueline N JN Lariviere William R WR Wallace Margaret R MR Sternberg Wendy F WF Balaban Carey D CD Belfer Inna I Fillingim Roger B RB

Nature neuroscience 20111023 12

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 analo ...[more]

PMID: 22019732

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Dataset Information

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

Publications

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

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