Genetic influences in opioid analgesic sensitivity in mice.
Studies of various strains of mice revealed marked differences in their analgesic sensitivity towards morphine (mu), U50,488H (kappa 1) and naloxone benzoylhydrazone (NalBzoH; kappa 3). Sensitivity to mu and kappa analgesia varied independently of the other. Analgesic sensitivity to morphine remained relatively consistent among 3 different nociceptive assays for each strain. However, the sensitivity of an individual strain to NalBzoH remained highly dependent upon the assay used. CD-1 mice were sensitive to NalBzoH in all 3 assays, but in BALB/c mice NalBzoH produced analgesia only in the hot plate and cold water tail-flick assays. In Swiss-Webster mice, NalBzoH was active in the radiant heat and cold water tail-flicks but inactive in the hot plate. Although the levels of mu, kappa 1 and kappa 3 binding in whole brain homogenates did vary somewhat, they did not correlate with analgesic sensitivity. These results suggests that the genetic controls over mu and kappa analgesia operate independently and further illustrate the many difficulties in evaluating potential analgesics.
Pick
C G
CG
Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Cheng
J
J
Paul
D
D
Pasternak
G W
GW
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013045:Species Specificity
D000700:Analgesics; D044482:Benzeneacetamides; D004745:Enkephalins; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C058380:naloxone benzoylhydrazone; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C045444:U 69593