Changes in analgesia-producing mechanism of repeated cold stress loading in mice.
Functional changes in opioid receptors involved in analgesia of repeated cold stress (RCS)-loaded mice were investigated. The antinociceptive potency of morphine (4 mg/kg, PO) was not affected in normal mice by norbinaltorphimine (10 mg/kg, SC), but treatment with this agent resulted in a lower level of morphine-induced antinociception in RCS-loaded animals. The antinociceptive activity of U-50488H (3 mg/kg, SC) was increased in RCS-loaded mice. In contrast to hypersensitivity to U-50488H (1 and 10 microg, IT) noted in RCS-loaded mice, the antinociception induced by DAMGO (0.1 and 1 microg, ICV) was reduced compared to that of normal animals. Diazepam (1 mg/kg/day SC) was given during RCS loading, and this agent prevented the development of hyperalgesia and the decrease in the antinociceptive activity of DAMGO (1 microg, ICV) in RCS-loaded mice, but there was no effect on the enhancement of the antinociceptive potency of U-50488H (10 microg, IT). These results indicate that the RCS-loaded mice were hyposensitive to supraspinal mu-opioid receptor-mediated antinociception, whereas their antinociceptive activities through kappa-opioid receptor in the spinal cord were increased. Hypofunction of the supraspinal mu-opioid receptor due to anxiety may explain the mechanism involved in the lowering of the nociceptive threshold in RCS-loaded animals.
Omiya
Y
Y
Kampo and Pharmacognosy Laboratories, Tsumura & Co., Ibaraki, Japan.
Goto
K
K
Ishige
A
A
Komatsu
Y
Y
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D003080:Cold Temperature / Q000009:adverse effects*; D003975:Diazepam / Q000494:pharmacology* / Q000627:therapeutic use; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects*; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013312:Stress, Physiological / Q000503:physiopathology*
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D014151:Anti-Anxiety Agents; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D003975:Diazepam