Targeting pain-depressed behaviors in preclinical assays of pain and analgesia: drug effects on acetic acid-depressed locomotor activity in ICR mice.
Targeting pain-depressed behaviors in preclinical assays of pain and analgesia: drug effects on acetic acid-depressed locomotor activity in ICR mice.
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DOI：
10.1016/j.lfs.2009.06.006
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发表时间：
2009-08-12
期刊：
影响因子：
6.1
通讯作者：
Bilsky, Edward J.
中科院分区：
文献类型：
--
作者：
Stevenson, Glenn W.;Cormier, Jim;Mercer, Hannah;Adams, Chloe;Dunbar, Catherine;Negus, S. Stevens;Bilsky, Edward J.
关键词：
疼痛抑制了许多行为的表达，而止痛治疗的目标之一就是恢复疼痛抑制的行为。专注于疼痛抑制行为的分析可能有助于对候选止痛药的临床前评估。本研究比较了MU阿片受体激动剂吗啡、多巴胺受体拮抗剂氟哌啶醇、腺苷受体拮抗剂咖啡因和神经激肽-1受体拮抗剂CJ 11,974-01对醋酸诱导的雄性ICR小鼠扭体(传统的疼痛刺激行为)和醋酸诱导的运动活动抑制(疼痛抑制行为)的影响。药物对非抑郁(基线)活动的影响也被检测。腹腔注射冰醋酸(0.18-1%)刺激小鼠扭体反应和抑制小鼠的活动能力相当。吗啡既能阻断酸诱导的扭体刺激，也能抑制运动抑制，尽管在酸抑制的运动测试中，吗啡的效力要低56倍。氟哌啶醇和CJ11,974-01可减少酸引起的扭体反应，但不能阻断酸引起的运动抑制。咖啡因对酸刺激的扭体或酸抑制的运动活动没有影响，尽管它确实增加了非抑郁的运动。因此，吗啡是唯一一种既能阻断酸刺激的扭体运动又能阻断酸抑制的运动的药物。疼痛刺激和疼痛抑制行为的互补分析可能会提高评估候选止痛药的临床前研究的预测有效性。吗啡对酸诱导的运动抑制的阻断力很低，这表明运动活动可能是研究疼痛抑郁行为的相对不敏感的指标。
Pain depresses expression of many behaviors, and one goal of analgesic treatment is to restore pain-depressed behaviors. Assays that focus on pain-depressed behaviors may contribute to preclinical assessment of candidate analgesics. This study compared effects of the mu opioid receptor agonist morphine (an acknowledged analgesic), the dopamine receptor antagonist haloperidol (a non-analgesic sedative), the adenosine receptor antagonist caffeine (a non-analgesic stimulant) and the neurokinin-1 receptor antagonist CJ 11,974-01 (a candidate analgesic) on acetic acid-induced writhing (a traditional pain-stimulated behavior) and acetic acid-induced suppression of locomotor activity (a pain-depressed behavior) in male ICR mice. Drug effects on non-depressed (baseline) locomotor activity were also examined. I.P. administration of acetic acid (0.18-1%) was equipotent in stimulating writhing and depressing locomotor activity. Morphine blocked both acid-induced stimulation of writhing and depression of locomotion, although it was 56-fold less potent in the assay of acid-depressed locomotion. Haloperidol and CJ 11,974-01 decreased acid-stimulated writhing, but failed to block acid-induced depression of locomotion. Caffeine had no effect on acid-stimulated writhing or acid-depressed locomotor activity, although it did increase non-depressed locomotion. Thus, morphine was the only drug to block both acid-stimulated writhing and acid-depressed locomotion. Complementary assays of pain-stimulated and pain-depressed behaviors may improve the predictive validity of preclinical studies that assess candidate analgesic drugs. The low potency of morphine to block acid-induced depression of locomotion suggests that locomotor activity may be a relatively insensitive measure for studies of pain-depressed behavior.
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影响因子：
2.9
作者：
MICHAELTITUS, A;DOURMAP, N;COSTENTIN, J
通讯作者：
COSTENTIN, J
影响因子：
1.6
作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1124/jpet.104.082966
发表时间：
2005-06-01
影响因子：
3.5
作者：
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通讯作者：
Bilsky, EJ
影响因子：
13.8
作者：
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通讯作者：
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