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 journalArticlepeer-review

374 Scopus citations


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
Issue number6600
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • General


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