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

Research output: Contribution to journalArticle

355 Citations (Scopus)

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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Aggression
Anxiety
Enkephalins
Pain
Analgesia
Pain Perception
Protein Precursors
Opioid Peptides
Homologous Recombination
Embryonic Stem Cells
Opioid Analgesics
Genotype
Genes
preproenkephalin

ASJC Scopus subject areas

  • General

Cite this

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

Pain responses, anxiety and aggression in mice deficient in pre- proenkephalin. / Konig, M.; Zimmer, A. M.; Steiner, H.; Holmes, P. V.; Crawley, Jacqueline; Brownstein, M. J.; Zimmer, A.

In: Nature, Vol. 383, No. 6600, 1996, p. 535-538.

Research output: Contribution to journalArticle

Konig, M, Zimmer, AM, Steiner, H, Holmes, PV, Crawley, J, Brownstein, MJ & Zimmer, A 1996, 'Pain responses, anxiety and aggression in mice deficient in pre- proenkephalin', Nature, vol. 383, no. 6600, pp. 535-538. https://doi.org/10.1038/383535a0
Konig M, Zimmer AM, Steiner H, Holmes PV, Crawley J, Brownstein MJ et al. Pain responses, anxiety and aggression in mice deficient in pre- proenkephalin. Nature. 1996;383(6600):535-538. https://doi.org/10.1038/383535a0
Konig, M. ; Zimmer, A. M. ; Steiner, H. ; Holmes, P. V. ; Crawley, Jacqueline ; Brownstein, M. J. ; Zimmer, A. / Pain responses, anxiety and aggression in mice deficient in pre- proenkephalin. In: Nature. 1996 ; Vol. 383, No. 6600. pp. 535-538.
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