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

M. Konig, A. M. Zimmer, H. Steiner, P. V. Holmes, Jacqueline Crawley, M. J. Brownstein, A. Zimmer

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360 Scopus citations

Abstract

ENKEPHALINS are endogenous opioid peptides that are derived from a pre- proenkephalin precursor protein. They are thought to be vital in regulating many physiological functions, including pain perception and analgesia, responses to stress, aggression and dominance. Here we have used a genetic approach to study the role of the mammalian opioid system. We disrupted the preproenkephalin 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.

Original languageEnglish (US)
Pages (from-to)535-538
Number of pages4
JournalNature
Volume383
Issue number6600
DOIs
StatePublished - 1996
Externally publishedYes

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    Konig, M., Zimmer, A. M., Steiner, H., Holmes, P. V., Crawley, J., Brownstein, M. J., & Zimmer, A. (1996). Pain responses, anxiety and aggression in mice deficient in pre- proenkephalin. Nature, 383(6600), 535-538. https://doi.org/10.1038/383535a0