Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin.
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.
König
M
M
Unit on Developmental Biology, Laboratory of Cell Biology, Section on Neuroanatomy, Laboratory of Neurophysiology, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Zimmer
A M
AM
Steiner
H
H
Holmes
P V
PV
Crawley
J N
JN
Brownstein
M J
MJ
Zimmer
A
A
D000374:Aggression; D000698:Analgesia; D000818:Animals; D001007:Anxiety / Q000235:genetics; D002460:Cell Line; D004745:Enkephalins / Q000172:deficiency / Q000502:physiology*; D005260:Female; D018390:Gene Targeting; D006720:Homozygote; D008297:Male; D051379:Mice; D016296:Mutagenesis; D010146:Pain; D011498:Protein Precursors / Q000172:deficiency / Q000502:physiology*; D015183:Restriction Mapping
D004745:Enkephalins; D011498:Protein Precursors; C033660:preproenkephalin