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TY - JOUR AU - König, Monika AU - Zimmer, Anne M. AU - Steiner, Heinz AU - Holmes, Philip V. AU - Crawley, Jacqueline N. AU - Brownstein, Michael J. AU - Zimmer, Andreas PY - 1996 DA - 1996/10/01 TI - Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin JO - Nature SP - 535 EP - 538 VL - 383 IS - 6600 AB - ENKEPHALINS are endogenous opioid peptides that are derived from a pre-proenkephalin precursor protein1,2. They are thought to be vital in regulating many physiological functions, including pain perception and analgesia, responses to stress, aggression and dominance3–5. 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. SN - 1476-4687 UR - https://doi.org/10.1038/383535a0 DO - 10.1038/383535a0 ID - König1996 ER -