ArticlesChanges in Analgesia-Producing Mechanism of Repeated Cold Stress Loading in Mice
Section snippets
Animals
Male ddY mice weighing 20–25 g at the beginning of the experiment were used. Four animals were housed per cage under a 12-h light and dark cycle (lights on between 0700–1900) and had free access to food and water throughout the experiments.
Repeated Cold Stress (RCS)
Kuraishi et al. (15) reported that sufficient and constant decreases in the nociceptive threshold were induced 3 days after initiation of RCS loading. In our experiment, the nociceptive threshold was also decreased 3 days after initiation of RCS-loading (Fig.
Effects of nor-BNI on the Antinociceptive Action of Morphine in RCS-Loaded and Normal Mice
The antinociceptive effect of morphine (4 mg/kg, PO), was not affected by RCS loading. Pretreatment with nor-BNI (10 mg/kg, SC), a highly selective antagonist of κ-opioid receptors, did not influence the antinociceptive effects of morphine in the normal (untreated) mice, whereas it reduced the potency of morphine-induced analgesia to 51% of that in the saline-treated group in RCS-loaded mice (Fig. 2).
Effects of RCS Loading on the Antinociceptive Activity of U-50488H
The antinociceptive activity of U-50488H (3 mg/kg, SC), a κ-opioid agonist, in the RCS-loaded
Discussion
This study is the first report demonstrating hyporesponsiveness of the supraspinal μ-opioid receptors and the enhancement of the spinal κ-opioid receptor-mediated antinociception in RCS-loaded animals.
The antinociceptive activity of morphine was decreased by pretreatment with nor-BNI in RCS mice, indicating that nearly half of the activity might be mediated by κ-opioid receptors in those animals. The increase in the antinociceptive activity of U-50488H in RCS-loaded mice supported that the role
Acknowledgements
This study was supported by Aging and Health research funds from the Ministry of Health and Welfare.
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