Amelioration of the reduced antinociceptive effect of morphine in the unpredictable chronic mild stress model mice by noradrenalin but not serotonin reuptake inhibitors.
Amelioration of the reduced antinociceptive effect of morphine in the unpredictable chronic mild stress model mice by noradrenalin but not serotonin reuptake inhibitors.
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DOI：
10.1186/s12990-015-0051-0
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发表时间：
2015-08-11
期刊：
影响因子：
3.3
通讯作者：
Satoh M
中科院分区：
文献类型：
--
作者：
Ide S;Satoyoshi H;Minami M;Satoh M
虽然在压力条件下，阿片类药物的疼痛敏感性和镇痛作用都发生了改变，但不可预测的慢性轻度压力（UCMS）对阿片类镇痛药的抗伤害作用的影响仍有待充分研究。本研究观察了UCMS对两种阿片类镇痛药吗啡（阿片受体激动剂）和曲马多（μ-阿片受体激动剂和去甲肾上腺素和5-羟色胺转运体抑制剂）的热痛敏感性和抗伤害作用的影响。我们还研究了预处理与马普替林（去甲肾上腺素再摄取抑制剂）和艾司西酞普兰（5-羟色胺再摄取抑制剂）对吗啡的抗伤害作用在小鼠UCMS条件下的影响。在小鼠热板试验中，不可预测的慢性轻度应激并不影响基础热痛敏感性。尽管吗啡在UCMS和非应激条件下均呈剂量依赖性地诱导热镇痛效应，但在UCMS条件下3 mg/kg吗啡的热镇痛效应显著低于非应激条件下。与吗啡的情况不同，我们观察到曲马多在UCMS和非应激条件下的热抗伤害作用无显著差异。此外，用10 mg/kg马普替林预处理可显著改善UCMS条件下3 mg/kg吗啡降低的热抗伤害效应，但3 mg/kg艾司西酞普兰不能。单独使用马普替林或艾司西酞普兰预处理在任一条件下均与抗伤害感受作用无关。我们证明了吗啡的抗伤害效应在经历UCMS的小鼠中降低，而曲马多没有。在UCMS条件下，吗啡的抗伤害作用降低，但依他普仑不能通过马普替林预处理来改善。这些结果表明，慢性应激条件下吗啡的抗伤害性作用的减少可能是通过激活去甲肾上腺素能系统而不是去甲肾上腺素能系统来改善的。
Although alterations in not only the pain sensitivity but also the analgesic effects of opioids have been reported under conditions of stress, the influence of unpredictable chronic mild stress (UCMS) on the antinociceptive effects of opioid analgesics remains to be fully investigated. The present study examined the influence of UCMS on the thermal pain sensitivity and antinociceptive effects of two opioid analgesics, morphine (an agonist of opioid receptors) and tramadol (an agonist of μ-opioid receptor and an inhibitor of both noradrenaline and serotonin transporters). We also examined the effects of pretreatment with maprotiline (a noradrenaline reuptake inhibitor) and escitalopram (a serotonin reuptake inhibitor) on the antinociceptive action of morphine in mice under an UCMS condition. Unpredictable chronic mild stress did not affect the basal thermal pain sensitivity in a mouse hot-plate test. Although morphine dose-dependently induced thermal antinociceptive effects under both the UCMS and non-stress conditions, the thermal antinociceptive effect of 3 mg/kg morphine under the UCMS condition was significantly lower than under the non-stressed condition. Unlike the case with morphine, we observed no significant difference in the thermal antinociceptive effect of tramadol between the UCMS and non-stress conditions. Furthermore, the reduced thermal antinociceptive effect of 3 mg/kg morphine under the UCMS condition was significantly ameliorated by pretreatment with 10 mg/kg maprotiline but not 3 mg/kg escitalopram. Pretreatment with neither maprotiline nor escitalopram alone was associated with an antinociceptive effect under either condition. We demonstrated that the antinociceptive effect of morphine but not tramadol was reduced in mice that had experienced UCMS. The reduced antinociceptive effect of morphine under the UCMS condition was ameliorated by pretreatment with maprotiline but not escitalopram. These results suggest that the reduced antinociceptive effects of morphine under conditions of chronic stress may be ameliorated by activation of the noradrenergic but not the serotonergic system.