Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function.
Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function.
复制标题
炎症引起的大鼠炎症引起的家用笼子抑制的分析揭示了阿片类药物抗伤害感和功能恢复之间的差异。
DOI：
10.1016/j.bbr.2016.10.024
复制
发表时间：
2017-01-15
影响因子：
2.7
通讯作者：
Morgan, Michael M.
中科院分区：
文献类型：
--
作者：
Kandasamy, Ram;Calsbeek, Jonas J.;Morgan, Michael M.
阿片类药物可有效抑制啮齿动物对有害刺激的反应，但对慢性疼痛患者的疗效有限且有许多副作用。这种脱节的一个原因是，伤害性感受通常是通过动物对伤害性刺激的退缩来评估的，而慢性疼痛患者遭受的是破坏正常活动的异常疼痛。我们假设，对大鼠在笼中跑轮的评估将提供一种更具临床相关性的方法来评估阿片类药物恢复正常行为的疗效。足底注射完全弗氏佐剂（CFA）到右后爪压低轮运行，并引起机械性异常性疼痛测量与冯弗雷测试在男性和女性大鼠。给予ED 50剂量的吗啡（3.2 mg/kg）可逆转机械性异常性疼痛，但不能逆转CFA诱导的车轮运行抑制。与此相反，低剂量吗啡（1.0毫克/公斤）的管理恢复运行一个小时，在两种性别，但没有影响机械异常性疼痛。非典型阿片类药物丁丙诺啡的管理没有影响炎症诱导的抑郁症的车轮运行在雄性或雌性大鼠，但衰减机械异常性疼痛的雄性大鼠。给予丁丙诺啡和更高剂量的吗啡抑制了非炎症大鼠的轮跑，这表明阿片类药物的副作用干扰了功能的恢复。这些数据表明，疼痛抑制功能的恢复需要在没有破坏性副作用的情况下进行抗伤害感受。阿片类药物的破坏性副作用与阿片类药物在人类疼痛患者中使用的主要限制一致。
Opioids are effective at inhibiting responses to noxious stimuli in rodents, but have limited efficacy and many side effects in chronic pain patients. One reason for this disconnect is that nociception is typically assessed using withdrawal from noxious stimuli in animals, whereas chronic pain patients suffer from abnormal pain that disrupts normal activity. We hypothesized that assessment of home cage wheel running in rats would provide a much more clinically relevant method to assess opioid efficacy to restore normal behavior. Intraplantar injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw depressed wheel running and caused mechanical allodynia measured with the von Frey test in both male and female rats. Administration of an ED50 dose of morphine (3.2 mg/kg) reversed mechanical allodynia, but did not reverse CFA-induced depression of wheel running. In contrast, administration of a low dose of morphine (1.0 mg/kg) restored running for one hour in both sexes, but had no effect on mechanical allodynia. Administration of the atypical opioid buprenorphine had no effect on inflammation-induced depression of wheel running in male or female rats, but attenuated mechanical allodynia in male rats. Administration of buprenorphine and higher doses of morphine depressed wheel running in non-inflamed rats, suggesting that the side effects of opioids interfere with restoration of function. These data indicate that restoration of pain-depressed function requires antinociception in the absence of disruptive side effects. The disruptive side effects of opioids are consistent with the major limitation of opioid use in human pain patients.
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影响因子：
7.4
作者：
Negus SS;Neddenriep B;Altarifi AA;Carroll FI;Leitl MD;Miller LL
通讯作者：
Miller LL
影响因子：
2.9
作者：
EIKELBOOM, R;MILLS, R
通讯作者：
MILLS, R
DOI：
10.1124/jpet.114.219873
发表时间：
2015-02-01
影响因子：
3.5
作者：
Altarifi, Ahmad A.;Rice, Kenner C.;Negus, S. Stevens
通讯作者：
Negus, S. Stevens
影响因子：
3.2
作者：
Gatti, Antonio;Dauri, Mario;Sabato, Alessandro Fabrizio
通讯作者：
Sabato, Alessandro Fabrizio
DOI：
10.1523/jneurosci.4123-08.2008
发表时间：
2008-12-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Loyd DR;Wang X;Murphy AZ
通讯作者：
Murphy AZ