Fletcher D, Kayser V, Guilbaud G
Départment d'Anesthésie Réanimation, Hôpital Bicêtre, France.
Anesthesiology. 1996 May;84(5):1129-37. doi: 10.1097/00000542-199605000-00015.
Recent evidence has suggested that the timing of administration of analgesic drugs could influence their efficacy by reducing the sensitization of the nervous system induced by the nociceptive inputs, but this concept of preemptive analgesia is still debated in both clinical and basic research.
The model of acute inflammatory pain induced by carrageenin was used to study the influence of timing of administration of bupivacaine (0.2 ml of a 0.5% solution with 0.005 mg/ml epinephrine) on the development of hyperalgesia, edema, and increase in temperature. The animals received bupivacaine 5 min before (BUPI PRE group, n = 20) or 60 min after (BUPI POST group, n = 20) carrageenin (1 ml/kg of 1% solution) was injected into the left hind paw. Two control groups (n = 15 in each) received saline 5 min before or 60 min after administration of carrageenin. Hyperalgesia of the injected paw was evaluated by the vocalization threshold to paw pressure, edema by measuring paw circumference with a thread, and plantar temperature with a thermocouple thermometer. All measurements were done before carrageenin injection then every 30 min thereafter for 240 min. Another series (n = 24), with the same four groups was also evaluated at 24 h.
Local injection of bupivacaine 60 min after carrageenin partially reduced the edema and hyperalgesia. The injection of bupivacaine 5 min before carrageenin was more efficient than the delayed injection and reduced hyperalgesia, edema and the increase in temperature temporarily, but did not totally prevent their development. All groups were similar at 240 min and 24 h.
These results show that a slight advantage of infiltration with bupivacaine before injury exists in this carrageenin model of acute inflammatory pain. However, this benefit is limited in time and bupivacaine did not have any preemptive analgesic effect.
最近有证据表明，镇痛药的给药时机可能通过减少伤害性输入引起的神经系统敏化来影响其疗效，但这种超前镇痛的概念在临床和基础研究中仍存在争议。
采用角叉菜胶诱导的急性炎性疼痛模型，研究布比卡因（0.2 ml含0.005 mg/ml肾上腺素的0.5%溶液）给药时机对痛觉过敏、水肿和体温升高的影响。动物在角叉菜胶（1 ml/kg 1%溶液）注入左后爪前5分钟（布比卡因预处理组，n = 20）或后60分钟（布比卡因后处理组，n = 20）接受布比卡因。两个对照组（每组n = 15）在角叉菜胶给药前5分钟或后60分钟接受生理盐水。通过对爪部压力的发声阈值评估注射爪的痛觉过敏，用线测量爪周长评估水肿，用热电偶温度计测量足底温度。所有测量均在注射角叉菜胶前进行，此后每30分钟进行一次，共240分钟。另一组（n = 24），同样的四组也在24小时时进行评估。
角叉菜胶注射后60分钟局部注射布比卡因可部分减轻水肿和痛觉过敏。角叉菜胶注射前5分钟注射布比卡因比延迟注射更有效，可暂时减轻痛觉过敏、水肿和体温升高，但不能完全阻止其发展。所有组在240分钟和24小时时相似。
这些结果表明，在这个角叉菜胶诱导的急性炎性疼痛模型中，损伤前用布比卡因浸润有轻微优势。然而，这种益处是有限的，布比卡因没有任何超前镇痛作用。
