Eisenberg Elon, McNicol Ewan D, Carr Daniel B
Pain Relief Unit, Rambam Medical Center, Haifa Pain Research Group, the Technion-Israel Institute of Technology, P.O. Box 9602, Haifa 31096, Israel.
Eur J Pain. 2006 Nov;10(8):667-76. doi: 10.1016/j.ejpain.2005.10.007. Epub 2005 Dec 5.
Several reviews of randomized controlled trials (RCTs) have shown the efficacy of mu-opioids in reducing spontaneous neuropathic pain (NP). However, relatively little is known about their specific efficacy for evoked pain, which is a significant problem for many patients with NP. The present systematic review assesses the efficacy of opioid agonists for the treatment of evoked NP based upon published RCTs. We searched articles in any language using the MEDLINE database (1966 to December 2004), the Cochrane Central Register of Controlled Trials (4th quarter, 2004) and the reference lists of retrieved papers, employing search terms for RCTs, opioids and NP. Only RCTs in which opioid agonists were given to treat NP of any etiology, and evoked pain was assessed were included. Data were extracted by two independent investigators. Nine articles met inclusion criteria and were classified as short-term (less than 24h; n=7) or intermediate-term trials (4 weeks; n=2). Although the scarcity of retrieved data precluded formal meta-analysis of short-term trials, we found that the intensity of dynamic mechanical allodynia was significantly attenuated by opioids relative to placebo in all studies. In contrast, no consistent effects on the magnitude of static allodynia, the threshold for mechanical allodynia or the threshold or magnitude of heat allodynia were found. The threshold and magnitude of cold-induced allodynia generally responded positively to opioid treatments in patients with peripheral pain syndromes, but not central pain syndromes. Evoked pain was studied in only two intermediate-term trials, in both of which oxycodone was significantly superior to placebo. The results of the two trials were combinable for a meta-analysis that showed an overall 24 points difference in endpoint pain intensities between patients given opioids and those treated with placebo (95% CI -33 to -15; p<0.00001).
short-term studies show that opioids can reduce the intensity of dynamic mechanical allodynia and perhaps of cold allodynia in peripheral NP. Insufficient evidence precludes drawing conclusions regarding the effect of opioids on other forms of evoked NP. A meta-analysis of intermediate-term studies demonstrates the efficacy of opioids over placebo for evoked NP. These findings are clinically relevant because dynamic mechanical allodynia and cold allodynia are the most prevalent types of evoked pain in NP.
多项随机对照试验（RCT）综述表明，μ阿片类药物在减轻自发性神经病理性疼痛（NP）方面具有疗效。然而，对于其对诱发性疼痛的具体疗效了解相对较少，而诱发性疼痛是许多NP患者面临的一个重要问题。本系统综述基于已发表的RCT评估阿片类激动剂治疗诱发性NP的疗效。我们使用MEDLINE数据库（1966年至2004年12月）、Cochrane对照试验中央注册库（2004年第4季度）以及检索论文的参考文献列表，以任何语言检索文章，使用RCT、阿片类药物和NP的检索词。仅纳入给予阿片类激动剂治疗任何病因的NP且评估了诱发性疼痛的RCT。数据由两名独立研究者提取。九篇文章符合纳入标准，分为短期试验（少于24小时；n = 7）或中期试验（4周；n = 2）。尽管检索到的数据有限，无法对短期试验进行正式的荟萃分析，但我们发现，在所有研究中，相对于安慰剂，阿片类药物可显著减轻动态机械性异常性疼痛的强度。相比之下，未发现对静态异常性疼痛的程度、机械性异常性疼痛的阈值或热异常性疼痛的阈值或程度有一致影响。在周围性疼痛综合征患者中，冷诱导的异常性疼痛的阈值和程度通常对阿片类药物治疗有阳性反应，但在中枢性疼痛综合征患者中则不然。仅在两项中期试验中研究了诱发性疼痛，在这两项试验中，羟考酮均显著优于安慰剂。两项试验的结果可合并进行荟萃分析，结果显示，给予阿片类药物的患者与接受安慰剂治疗的患者在终点疼痛强度上总体相差24分（95%CI -33至-15；p<0.00001）。
短期研究表明，阿片类药物可减轻周围性NP中动态机械性异常性疼痛的强度，或许还能减轻冷异常性疼痛的强度。证据不足，无法就阿片类药物对其他形式的诱发性NP的影响得出结论。对中期研究的荟萃分析表明，阿片类药物治疗诱发性NP比安慰剂更有效。这些发现具有临床相关性，因为动态机械性异常性疼痛和冷异常性疼痛是NP中最常见的诱发性疼痛类型。
