School of Medical Sciences, University of New South Wales, NSW 2052, Australia Department of Neurology, Moscow Medical Academy, Moscow 119021, Russia Team "Pain", INSERM UMRS 975, CNRS UMR 7225, Faculté de Médecine UPMC, Université Pierre et Marie Curie, Paris, France.
Pain. 2011 Mar;152(3):676-686. doi: 10.1016/j.pain.2010.12.019. Epub 2011 Jan 28.
An increased tail-flick latency to noxious heat during or after stress in the rodent is usually interpreted as a stress-induced reduction in pain sensitivity and often described as a form of stress-induced "analgesia." However, this measure is an indirect and flawed measure of the change in nociceptive threshold to noxious heat. A major confound of the latency measure is the initial temperature of the tail, which can drop down to room temperature during stress, the consequence of a marked sympathetically mediated vasoconstriction in the skin of the extremities. We addressed this issue with tail-flick tests during contextual fear using infrared thermography to monitor temperature changes and a CO2 laser to deliver the heat stimulus. The experiment revealed a 4.2°C increase of the nociceptive threshold, confirming a true antinociceptive effect. However, its contribution to the increased withdrawal latency was less than two-thirds (63.2%). Nearly one-third (32.2%) was due to the drop in tail temperature (4.4°C), which also slowed conduction along sensory fibers (2.2%, included in the 32.2%). The remaining 4.6% was due to an increase in decisional/motor latency. This new unbiased method establishes beyond doubt that a conditioned stress response is associated with true antinociception to noxious heat. It also confirms that stress-induced changes in skin temperature can be a major confound in tail-flick tests. The present study shows, for the first time, the exact contribution of these two components of the tail-flick latency for a stress response. Less than two-thirds of the increase in tail-flick latency to noxious heat, evoked by conditioned fear, reflects true antinociception. The remaining is due to skin vasoconstriction.
在啮齿动物中，应激过程中或应激后对有害热刺激的甩尾潜伏期延长通常被解释为应激引起的疼痛敏感性降低，通常被描述为应激诱导的“镇痛”形式。然而，这种测量方法是对有害热刺激的伤害感受阈值变化的间接和有缺陷的测量。潜伏期测量的一个主要混杂因素是尾巴的初始温度，在应激过程中，尾巴的初始温度可能会下降到室温，这是由于四肢皮肤明显的交感神经介导的血管收缩所致。我们使用红外热成像技术在情境性恐惧的甩尾测试中解决了这个问题，以监测温度变化，并使用二氧化碳激光来传递热刺激。实验显示，伤害感受阈值增加了 4.2°C，证实了真正的抗伤害作用。然而，它对延长的退缩潜伏期的贡献不到三分之二（63.2%）。近三分之一（32.2%）归因于尾巴温度的下降（4.4°C），这也减缓了感觉纤维的传导（2.2%，包含在 32.2%中）。剩下的 4.6%归因于决策/运动潜伏期的增加。这种新的无偏方法毫无疑问地证明，条件性应激反应与有害热刺激的真正镇痛作用有关。它还证实，应激引起的皮肤温度变化可能是甩尾测试中的一个主要混杂因素。本研究首次显示了条件性恐惧引起的有害热刺激甩尾潜伏期的这两个组成部分的确切贡献。对有害热刺激的甩尾潜伏期增加的不到三分之二反映了真正的镇痛作用。其余的是由于皮肤血管收缩。
