Pedersen J L, Kehlet H
Department of Surgical Gastroenterology, Hvidovre University Hospital, Denmark.
Pain. 1998 Feb;74(2-3):139-51. doi: 10.1016/s0304-3959(97)00160-7.
The aim of the study was to examine reproducibility of primary and secondary hyperalgesia in a psychophysical model of human inflammatory pain. Mild burns were produced on the crura of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Assessments of (i) cold and warm detection thresholds, (ii) mechanical and heat pain thresholds, (iii) pain to heat (43 degrees C and 45 degrees C, 5 s), (iv) secondary hyperalgesia, and (v) skin erythema were made 1.75 and 0.5 h before, and 0, 1, 2, 4, and 6 h after a burn injury. Sensory thresholds and hyperalgesia to heat and mechanical stimuli were examined by contact thermodes and von Frey hairs, and pain intensity was rated with a visual analog scale (0-100). To describe between-day reproducibility, the subjects were examined three times at intervals of 21 days. Within-day comparisons showed that a 20% change could be detected as significant for all variables with fewer than 12 subjects in a cross-over design (2alpha = 5% and power = 80%). Between-day comparisons demanded up to 25 subjects to detect changes of the same magnitude. The burns caused mild to moderate pain (VAS: mean 29, SD 14) and the subjects (all right-handed) were more sensitive to heat pain on their left side (P < 0.03). Hyperalgesia was induced instantaneously by the burn and outlasted the study period (6 h). However, no spontaneous pain was observed after the injury, and a brief period of hypoesthesia to warm and cold stimuli was induced by the burn. The painful measurements themselves evoked hyperalgesia to heat and mechanical stimuli on the arm, but only to mechanical stimuli on the legs. including secondary hyperalgesia. Hyperalgesia evoked by the measurements was significantly less intense than that induced by injury. Habituation to the painful stimuli was demonstrated by significantly higher pain thresholds and lower pain responses on the second and third day of the study. The burn model is a sensitive psychophysical model of acute inflammatory pain, when cross-over designs and within-day comparisons are used, and the model is suitable for double-blind, placebo-controlled studies of analgesics. In similar models, we recommend that analgesic and placebo are evenly divided between right and left sides and study days.
本研究的目的是在人类炎性疼痛的心理物理学模型中检验原发性和继发性痛觉过敏的可重复性。使用50×25毫米的热刺激器（47摄氏度，7分钟）对12名志愿者的小腿造成轻度烧伤。在烧伤前1.75小时和0.5小时，以及烧伤后0、1、2、4和6小时，对以下各项进行评估：（i）冷觉和温觉检测阈值；（ii）机械性和热痛阈值；（iii）对热（43摄氏度和45摄氏度，5秒）的疼痛；（iv）继发性痛觉过敏；（v）皮肤红斑。通过接触式热刺激器和von Frey毛发检查感觉阈值以及对热和机械刺激的痛觉过敏，并用视觉模拟量表（0 - 100）对疼痛强度进行评分。为了描述日间可重复性，让受试者每隔21天接受三次检查。日内比较表明，在交叉设计中，对于所有变量，当受试者少于12名时（双侧α = 5%，检验效能 = 80%），20%的变化可被检测为显著变化。日间比较则需要多达25名受试者才能检测到相同幅度的变化。烧伤引起轻度至中度疼痛（视觉模拟量表评分：平均29分，标准差14分），且受试者（均为右利手）左侧对热痛更敏感（P < 0.03）。烧伤瞬间诱发痛觉过敏，且持续超过研究期（6小时）。然而，损伤后未观察到自发痛，且烧伤诱发了对温热和冷刺激的短暂感觉减退期。疼痛测量本身诱发了手臂对热和机械刺激的痛觉过敏，但仅诱发了腿部对机械刺激的痛觉过敏，包括继发性痛觉过敏。测量诱发的痛觉过敏明显不如损伤诱发的强烈。研究的第二天和第三天，疼痛阈值显著升高，疼痛反应降低，证明了对疼痛刺激的适应性。当采用交叉设计和日内比较时，烧伤模型是一种敏感的急性炎性疼痛心理物理学模型，该模型适用于镇痛药的双盲、安慰剂对照研究。在类似模型中，我们建议将镇痛药和安慰剂在左右两侧以及研究日之间平均分配。
