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Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin

Nature volume 383, pages 535–538 (1996)Cite this article

Abstract

ENKEPHALINS are endogenous opioid peptides that are derived from a pre-proenkephalin precursor protein1,2. They are thought to be vital in regulating many physiological functions, including pain perception and analgesia, responses to stress, aggression and dominance3–5. Here we have used a genetic approach to study the role of the mammalian opioid system. We disrupted the pre-proenkephalin gene using homologous recombination in embryonic stem cells to generate enkephalin-deficient mice. Mutant enk−/− animals are healthy, fertile, and care for their offspring, but display significant behavioural abnormalities. Mice with the enk−/− genotype are more anxious and males display increased offensive aggressiveness. Mutant animals show marked differences from controls in supraspinal, but not in spinal, responses to painful stimuli. Unexpectedly, enk−/− mice exhibit normal stress-induced analgesia. Our results show that enkephalins modulate responses to painful stimuli. Thus, genetic factors may contribute significantly to the experience of pain.

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Author notes

  1. Heinz Steiner

    Present address: Department of Anatomy and Neurobiology, University of Tennessee, College of Medicine, Memphis, Tennessee, 38163, USA

  2. Philip V. Holmes

    Present address: Department of Psychology, University of Georgia, Athens, Georgia, 30602, USA

Authors and Affiliations

  1. Unit on Developmental Biology, Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland, 20892, USA

    Monika König, Anne M. Zimmer, Michael J. Brownstein & Andreas Zimmer

  2. Section on Neuroanatomy, Laboratory of Neurophysiology, National Institute of Mental Health, Bethesda, Maryland, 20892, USA

    Heinz Steiner

  3. Section on Behavioural Neuropharmacology, Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, Maryland, 20892, USA

    Philip V. Holmes & Jacqueline N. Crawley

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  1. Monika König
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König, M., Zimmer, A., Steiner, H. et al. Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin. Nature 383, 535–538 (1996). https://doi.org/10.1038/383535a0

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