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 language | English (US) |
|---|---|
| Pages (from-to) | 535-538 |
| Number of pages | 4 |
| Journal | Nature |
| Volume | 383 |
| Issue number | 6600 |
| DOIs | |
| State | Published - 1996 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Pain responses, anxiety and aggression in mice deficient in pre- proenkephalin
AU - Konig, M.
AU - Zimmer, A. M.
AU - Steiner, H.
AU - Holmes, P. V.
AU - Crawley, Jacqueline
AU - Brownstein, M. J.
AU - Zimmer, A.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0029957953&partnerID=8YFLogxK
U2 - 10.1038/383535a0
DO - 10.1038/383535a0
M3 - Article
C2 - 8849726
AN - SCOPUS:0029957953
VL - 383
SP - 535
EP - 538
JO - Nature
JF - Nature
SN - 0028-0836
IS - 6600
ER -