Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
J Pain. 2010 Mar;11(3):280-6. doi: 10.1016/j.jpain.2009.07.011. Epub 2009 Nov 27.
Noxious mechanical stimulation evokes a complex and sustained hyperalgesic motor response after peripheral nerve injury that contrasts with a brief and simple withdrawal seen after noxious stimulation in control animals or after threshold punctate mechanical stimulation by the von Frey technique. To test which of these behaviors indicate pain, the aversiveness of the experience associated with each was determined using a passive avoidance test in rats after sciatic nerve ligation (SNL) or skin incision alone. After 18 days, step-down latency was measured during 9 sequential trials at 10-minute intervals. At each trial, rats received either no stimulus, needle stimuli, or threshold Semmes Weinstein (SW) filament stimuli after stepping down. Reactions were either a hyperalgesic response or a brief reflexive withdrawal. In SNL animals, needle stimulation produced substantial learned avoidance when animals showed hyperalgesic responses but produced minimal prolonged latency in SNL animals that showed only simple withdrawal responses. No learned avoidance developed using threshold SW testing in SNL animals. These findings show that needle stimulation is aversive in rats responding with hyperalgesic behavior. In contrast, SW stimulation, as well as needle stimulation that produced mere withdrawal, is minimally aversive.
The validity of measures of pain in animals is open to question. We demonstrated that needle stimulation is aversive in rats that respond with hyperalgesic-type behavior and is therefore a valid indicator of pain. Stimulation by SW is minimally aversive and is a problematic indicator of pain.
在周围神经损伤后,有害的机械刺激会引起复杂而持续的痛觉过敏运动反应,与对照动物在有害刺激后或 von Frey 技术的阈点状机械刺激后看到的短暂而简单的退缩形成对比。为了测试这些行为中的哪一种表示疼痛,使用坐骨神经结扎 (SNL) 或单独皮肤切口后的被动回避测试来确定与每种行为相关的体验的厌恶程度。18 天后,在 9 次连续试验中,每隔 10 分钟测量一次跳下后的潜伏期。在每次试验中,老鼠要么接受无刺激,要么接受针刺激,要么在跳下后接受阈 Semmes Weinstein (SW) 纤维丝刺激。反应要么是痛觉过敏反应,要么是短暂的反射性退缩。在 SNL 动物中,当动物表现出痛觉过敏反应时,针刺激会产生大量的学习回避,但在仅表现出简单退缩反应的 SNL 动物中,针刺激只会产生最小的延长潜伏期。在 SNL 动物中,使用阈 SW 测试不会产生学习回避。这些发现表明,在表现出痛觉过敏行为的大鼠中,针刺激是令人厌恶的。相比之下,SW 刺激以及仅产生退缩的针刺激,令人厌恶的程度最小。
动物疼痛测量的有效性存在疑问。我们证明,在表现出痛觉过敏样行为的大鼠中,针刺激是令人厌恶的,因此是疼痛的有效指标。SW 刺激的刺激最小,是疼痛的一个有问题的指标。