Faculty of Medicine, Experimental Surgery Facility (ESF), Experimental Animal Center (EAC), University of Bern, Bern, Switzerland.
Faculty of Medicine, Department for BioMedical Research, University of Bern, Bern, Switzerland.
PLoS One. 2024 Aug 29;19(8):e0309604. doi: 10.1371/journal.pone.0309604. eCollection 2024.
Minipigs are widely used in biomedical research for translational studies. However, information about pain elicited by experimental procedures is lacking. Non-invasive methods as quantitative sensory testing and conditioned pain modulation are particularly attractive. Our overarching aim was to explore and refine these methods for assessing post-operative pain in minipigs after myocardial infarction. As first step, we aimed at defining mechanical and thermal thresholds in healthy adults Göttingen Minipigs, evaluating their reliability, and testing their modifications after the application of a conditioning stimulus. Thresholds were assessed at different body sites before and after a painful conditioning stimulus (CS) (cuffed tourniquet) and sham CS (uncuffed tourniquet) in eleven animals. Thresholds' reliability was assessed using interclass correlation coefficient (ICC). The effect of the CS was assessed calculating absolute change, percentage change of the thresholds and standard error of measurement. Baseline mechanical thresholds (Newton) were: left hindlimb 81 [73; 81]; left forearm 81 [72.1; 81]; right forearm 81 [76; 81]; left chest 80.5 [68; 81]; right chest 81 [76.5; 81]; left neck 81 [70.3; 81]; right neck 74.8 [62.3; 80.5]. Reliability of mechanical thresholds was good at right chest (ICC = 0.835) and moderate at left chest (ICC = 0.591), left hindlimb (ICC = 0.606) and left neck (ICC = 0.518). Thermal thresholds showed poor reliability in all the tested sites. A modulatory effect was present at right chest, but it was seen when both a painful CS and a sham CS was applied. Minipigs tendentially showed a pro-nociceptive profile (i.e. conditioning pain facilitation). The measured thresholds are a reference for future trials in this species. Mechanical thresholds showed to be more reliable and, therefore, more useful, than thermal ones. The pain facilitation might be explained by the phenomenon of stress induced hyperalgesia, but this finding needs to be further investigated with a stricter paradigm.
小型猪被广泛应用于转化医学的生物医学研究中。然而，对于实验操作引起的疼痛，相关信息还很缺乏。定量感觉测试和条件性疼痛调制等非侵入性方法特别有吸引力。我们的总体目标是探索和完善这些方法，以评估小型猪心肌梗死后的术后疼痛。作为第一步，我们旨在确定健康成年哥廷根小型猪的机械和热阈值，评估其可靠性，并测试在施加条件性刺激后其变化。在 11 只动物中，在施加疼痛性条件刺激（带袖口的止血带）和假条件刺激（不带袖口的止血带）前后，在不同的身体部位评估阈值。使用组内相关系数（ICC）评估阈值的可靠性。通过计算阈值的绝对变化、百分比变化和测量标准误差来评估条件刺激的效果。基线机械阈值（牛顿）为：左后肢 81 [73；81]；左前臂 81 [72.1；81]；右前臂 81 [76；81]；左胸 80.5 [68；81]；右胸 81 [76.5；81]；左颈 81 [70.3；81]；右颈 74.8 [62.3；80.5]。右胸的机械阈值可靠性良好（ICC = 0.835），左胸（ICC = 0.591）、左后肢（ICC = 0.606）和左颈（ICC = 0.518）的可靠性为中度。所有测试部位的热阈值可靠性均较差。在右胸存在调制效应，但在施加疼痛性 CS 和假 CS 时均可见。小型猪倾向于表现出伤害感受性增强的特征（即条件性疼痛易化）。所测量的阈值为该物种未来试验的参考。机械阈值比热阈值更可靠，因此更有用。这种疼痛易化可能是由应激诱导的痛觉过敏现象引起的，但这一发现需要通过更严格的范式进一步研究。
