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Nature. 1996 Oct 10;383(6600):535-8.

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

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

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 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.

PMID:
8849726
DOI:
10.1038/383535a0
[Indexed for MEDLINE]
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