Behavioral assessment of temporal summation in the rat: sensitivity to sex, opioids and modulation by NMDA receptor antagonists
Behavioral assessment of temporal summation in the rat: sensitivity to sex, opioids and modulation by NMDA receptor antagonists
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DOI：
10.1007/s00213-005-2153-2
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发表时间：
2005-06-01
影响因子：
3.4
通讯作者：
Picker, MJ
中科院分区：
文献类型：
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作者：
Lomas, LM;Picker, MJ
理由：疼痛的时间总和反映了在持续约 15 秒-2 分钟的重复伤害性刺激后，感知到的伤害性敏感性增加。这种伤害感受敏感性的短暂变化已被用作模型来检查影响疼痛中枢处理的因素以及某些慢性疼痛状况的潜在机制。目的：本研究的目的是开发一种行为程序来诱导大鼠的时间总和，并确定时间总和（即，在重复出现伤害性热刺激后减少尾部缩回潜伏期）对各种参数操作、性别、N-甲基-D-天冬氨酸（NMDA）受体系统的调节的敏感性，以及对阿片类药物逆转的敏感性。结果：时间总和的幅度通常随着伤害性刺激间间隔的增加而减小，并且随着伤害性刺激强度和伤害性刺激呈现次数的增加而增加。时间总和是短暂的，在最终伤害性刺激呈现后 3.0 秒内明显，但在 30 秒后不明显。男性的时间总和水平略高于女性。非竞争性 NMDA 拮抗剂氯胺酮 (3.0-30 mg/kg)、地佐环平 (0.03-0.1 mg/kg) 和右美沙芬 (10-30 mg/kg) 在未能产生抗伤害作用的剂量下减弱了时间总和水平（温水尾部撤回程序）。在抗伤害过程中，阿片类药物吗啡（3.0-10 mg/kg）、丁丙诺啡（0.3-3.0 mg/kg）、布托啡诺（3.0-30 mg/kg）和螺旋多林（10-30 mg/kg）对男性更有效，而这些阿片类药物在降低男性和女性的时间总和水平方面同样有效。结论：这些研究结果表明，人类和大鼠的时间总和的特征和受体调节存在许多相似之处，并且在这种慢性疼痛模型中，阿片类药物的效力不存在性别差异。
Rationale: Temporal summation of pain reflects a perceived increase in nociceptive sensitivity following repeated noxious stimulation that can last for similar to 15 s-2 min. This short-lasting change in nociceptive sensitivity has been used as a model to examine factors that influence the central processing of pain and the mechanisms underlying some chronic pain conditions. Objective: The purpose of this study was to develop a behavioral procedure to induce temporal summation in rats and determine the sensitivity of temporal summation (i. e., decrease tail-withdrawal latency following repeated presentations of a nociceptive thermal stimulus) to various parametric manipulations, sex, modulation by the N-methly-D-aspartate (NMDA) receptor system, and sensitivity to reversal by opioids. Results: The magnitude of temporal summation generally decreased with increases in the inter-nociceptive stimulus interval, and increased with increases in both the nociceptive stimulus intensity and the number of nociceptive stimulus presentations. Temporal summation was short-lived, evident 3.0 s after the final nociceptive stimulus presentation, but not after 30 s. Males displayed slightly higher levels of temporal summation than females. The non-competitive NMDA antagonists ketamine (3.0-30 mg/kg), dizocilpine (0.03-0.1 mg/kg) and dextromethorphan (10-30 mg/ kg) attenuated the level of temporal summation at doses that failed to produce antinociceptive effects (warm water tail-withdrawal procedure). In an antinociception procedure, the opioids morphine (3.0-10 mg/ kg), buprenorphine (0.3-3.0 mg/kg), butorphanol (3.0-30 mg/kg) and spiradoline (10-30 mg/kg) were more potent in males, whereas these opioids were equally potent and effective in reducing the level of temporal summation in males and females. Conclusions: These findings suggest a number of similarities in the characteristics and receptor modulation of temporal summation in humans and rats, and that in this model of chronic pain there are no sex differences in opioid potency.