The Differential Effect of Whole-body Irradiation on Morphine- and β-Endorphin-Induced Antinociceptive Actions in Mice
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Whole-body γ-irradiation(WBI), which produces an oxidative stress, is reported to attenuate the acute antinociceptive action of morphine (a μ-opioid receptor agonist), but not DPLPE (a δ-opioid receptor agonist), in mice. Recently, we also reported that antinociceptive effect of morphine, but not β-endorphin (a novel ε-opioid receptor agonist), was attenuated by oxidative stress. These findings prompted us to investigate the effect of WBI on the antinociception of morphine and β-endorphin in mice. Mice were exposed to WBI (5 Gy) from a 60 Co gamma-source and tested 2 hours later for antinociception produced by intracerebroventricular administration of morphine or β-endorphin using the hot water tail-immersion and the writhing tests. WBI significantly attenuated the antinociception produced by morphine only in the hot water tail-immersion test, whereas the antinociception of β-endorphin was significantly potentiated by WBI in both tests. These results demonstrate a differential sensitivity of μ- and ε-opioid receptors to WBI, and support the hypothesis that morphine and β-endorphin administered supraspinally produce antinociception by different neuronal mechanisms.
Abstract
Whole-body γ-irradiation(WBI), which produces an oxidative stress, is reported to attenuate the acute antinociceptive action of morphine (a μ-opioid receptor agonist), but not DPLPE (a δ-opioid receptor agonist), in mice. Recently, we also reported that antinociceptive effect of morphine, but not β-endorphin (a novel ε-opioid receptor agonist), was attenuated by oxidative stress. These findings prompted us to investigate the effect of WBI on the antinociception of morphine and β-endorphin in mice. Mice were exposed to WBI (5 Gy) from a 60 Co gamma-source and tested 2 hours later for antinociception produced by intracerebroventricular administration of morphine or β-endorphin using the hot water tail-immersion and the writhing tests. WBI significantly attenuated the antinociception produced by morphine only in the hot water tail-immersion test, whereas the antinociception of β-endorphin was significantly potentiated by WBI in both tests. These results demonstrate a differential sensitivity of μ- and ε-opioid receptors to WBI, and support the hypothesis that morphine and β-endorphin administered supraspinally produce antinociception by different neuronal mechanisms.
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