Wilder-Smith C H, Hill L, Spargo K, Kalla A
Visceral Physiology Institute, Groote Schuur Hospital, University of Cape Town, 7925, Cape Town, South Africa.
Pain. 2001 Mar;91(1-2):23-31. doi: 10.1016/s0304-3959(00)00414-0.
Opioids are increasingly used in the treatment of chronic non-malignant pain. The aim of this open-label, randomised, parallel group study was to compare analgesia and side-effects of two commonly used opioid analgesics, tramadol and dihydrocodeine, in long-acting formulations in 60 osteoarthritis patients with strong pain despite NSAID's. Dose titration based on effect was performed with the respective immediate release solutions given additionally to tramadol 100 mg bid and dihydrocodeine 60 mg bid during the first 4 days of the 1 month treatment. Electrical sensation and pain thresholds over the osteoarthritic joint and at a distant location and gastrointestinal transit times were performed before and during treatment. Thirty patients with pain controlled by NSAID's alone formed the comparator group. Pain intensities at rest and during movement decreased highly significantly with tramadol and dihydrocodeine from median pre-treatment verbal ratings of over 3 (0=none, 4=unbearable) to 1 and below from the second treatment day onwards (ANOVA P<0.0001). Pain at rest was significantly lower with tramadol (ANOVA P=0.04), but ratings were similar during movement. Mean (95% CI) daily doses on days 1 and 28 were 209 (198-220) mg and 203 (191-206) mg of tramadol, and 129 (122-136) mg and 130 (121-134) mg of dihydrocodeine, respectively. Minor side-effects were more common with tramadol (P=0.04). Changes in bowel functions and symptoms were minor with both treatments, but the frequency of defaecation was lower and stools were harder with dihydrocodeine. Orocaecal transit time remained unchanged and similar to controls with both analgesics. Colonic transit times only increased significantly during treatment with dihydrocodeine. Sensation and pain thresholds were lower pre-treatment in both groups than in controls and increased during treatment. These antinociceptive effects were more marked in the tramadol group and distant from the osteoarthritic joint. We conclude rapid pain relief was achieved with both long-acting tramadol and dihydrocodeine with NSAID's in strong osteoarthritis pain. Minimal dose titration was required and side-effects were minor. Tramadol interfered less with intestinal function and showed greater antinociceptive action.
阿片类药物越来越多地用于治疗慢性非恶性疼痛。这项开放标签、随机、平行组研究的目的是比较两种常用的阿片类镇痛药曲马多和双氢可待因长效制剂对60例尽管使用了非甾体抗炎药（NSAID）但仍有剧烈疼痛的骨关节炎患者的镇痛效果和副作用。在1个月治疗的前4天，在给予曲马多100mg bid和双氢可待因60mg bid的基础上，分别额外给予各自的速释溶液，并根据效果进行剂量滴定。在治疗前和治疗期间，测量骨关节炎关节及其远处的电感觉和疼痛阈值以及胃肠道转运时间。30例仅用NSAID控制疼痛的患者组成对照组。从治疗第二天起，曲马多和双氢可待因使静息和运动时的疼痛强度从治疗前的中位数口头评分超过3（0=无，4=难以忍受）显著降低至1及以下（方差分析P<0.0001）。曲马多使静息时的疼痛显著降低（方差分析P=0.04），但运动时的评分相似。第1天和第28天曲马多的平均（95%CI）日剂量分别为209（198-220）mg和203（191-206）mg，双氢可待因分别为129（122-136）mg和130（121-134）mg。曲马多的轻微副作用更常见（P=0.04）。两种治疗方法引起的肠道功能和症状变化都较小，但双氢可待因导致的排便频率较低且大便更硬。两种镇痛药的口盲肠转运时间均保持不变且与对照组相似。仅在双氢可待因治疗期间结肠转运时间显著增加。两组治疗前的感觉和疼痛阈值均低于对照组，且在治疗期间升高。这些抗伤害感受作用在曲马多组更明显，且远离骨关节炎关节。我们得出结论，长效曲马多和双氢可待因联合NSAID可迅速缓解重度骨关节炎疼痛。所需的剂量滴定最小，副作用较小。曲马多对肠道功能的干扰较小，且显示出更强的抗伤害感受作用。
