摘要

BACKGROUND: Postherpetic neuralgia (PHN) is a complication of acute herpes zoster, which is emerging as a preferred clinical trial model for chronic neuropathic pain. Although there are published meta-analyses of analgesic therapy in PHN, and neuropathic pain in general, the evidence base has been substantially enhanced by the recent publication of several major trials. Therefore, we have conducted a systematic review and meta-analysis for both efficacy and adverse events of analgesic therapy for PHN. METHODS AND FINDINGS: We systematically searched databases (MEDLINE 1966-2004, EMBASE 1988-2004, CINAHL 1982-2002, and PubMed [29 October 2004]) for trials of PHN. We also searched references of retrieved studies and review articles for further trials. We included trials that examined adult patients with PHN of greater duration than 3 mo, that were blinded, randomised, and had at least one measure of pain outcome. Dichotomous pain outcome data were extracted for 50% decrease in baseline pain using a hierarchy of pain/pain-relief measurement tools. Where available, dichotomous data were also collected for adverse events. Calculated estimates of efficacy included relative benefit and number needed to treat. Of 62 studies identified, 35 were randomised controlled trials. Of these, 31 were placebo controlled and suitable for meta-analysis, from which it was possible to extract dichotomous efficacy outcome data from 25. This meta-analysis revealed that there is evidence to support the use of the following orally administered therapies: tricyclic antidepressants, "strong" opioids, gabapentin, tramadol, and pregabalin. Topical therapies associated with efficacy were lidocaine 5% patch and capsaicin. Finally, a single study of spinal intrathecal administration of lidocaine and methyl prednisolone demonstrated efficacy, although this has yet to be replicated. Data suggest that the following therapies are not associated with efficacy in PHN: certain NMDA receptor antagonists (e.g., oral memantine, oral dextromethorphan, intravenous ketamine), codeine, ibuprofen, lorazepam, certain 5HT1 receptor agonists, and acyclovir. Topical administration of benzydamine, diclofenac/diethyl ether, and vincristine (iontophoresis) are similarly not associated with efficacy, nor are intrathecal administration of lidocaine alone or epidural administration of lidocaine and methylprednisolone, intravenous therapy with lidocaine, subcutaneous injection of Cronassial, or acupuncture. However, many of the trials that demonstrated a lack of efficacy represented comparatively low numbers of patient episodes or were single-dose studies, so it may be appropriate to regard such interventions as "not yet adequately tested" rather than demonstrating "no evidence of efficacy." Topical aspirin/diethyl ether has not been adequately tested. CONCLUSION: The evidence base supports the oral use of tricyclic antidepressants, certain opioids, and gabapentinoids in PHN. Topical therapy with lidocaine patches and capsaicin is similarly supported. Intrathecal administration of methylprednisolone appears to be associated with high efficacy, but its safety requires further evaluation.

译文

背景: 带状疱疹后遗神经痛 (PHN) 是急性带状疱疹的并发症，是治疗慢性神经病理性疼痛的首选临床试验模型。尽管已经发表了关于 PHN 镇痛治疗和一般神经性疼痛的荟萃分析，但最近发表的几项主要试验大大增强了证据基础。因此，我们对 PHN 镇痛治疗的疗效和不良事件进行了系统综述和荟萃分析。方法和结果: 我们系统地搜索了数据库 (MEDLINE 1966-2004 、 EMBASE 1988-2004 、 CINAHL 1982-2002 和 PubMed [2004年10月29日]) 的 PHN 试验。我们还搜索了检索到的研究的参考文献和综述文章，以进行进一步的试验。我们纳入了一些试验，这些试验检查了 PHN 持续时间大于 3 个月的成年患者，这些患者是盲法、随机的，并且至少有一项疼痛结果衡量标准。使用疼痛/疼痛缓解测量工具的层次结构提取了基线疼痛降低 50% 的二分疼痛结局数据。在可用的情况下，还收集了不良事件的二分数据。疗效的计算估计值包括相对益处和治疗所需的数量。在 62 项研究中，35 项是随机对照试验。其中，31 例为安慰剂对照，适用于荟萃分析，从中可以从 25 例中提取二分疗效结果数据。这项荟萃分析显示，有证据支持使用以下口服疗法: 三环抗抑郁药、 “强” 阿片类药物、加巴喷丁、曲马多和普瑞巴林。与疗效相关的局部治疗是利多卡因 5% 贴剂和辣椒素。最后，一项关于脊髓鞘内注射利多卡因和甲基强的松龙的单一研究证明了疗效，尽管这还没有被复制。数据表明以下疗法与 PHN 的疗效无关: 某些 NMDA 受体拮抗剂 (例如，口服美金刚、口服右旋甲沙芬、静脉注射氯胺酮) 、可待因、布洛芬、劳拉西泮、某些 5HT1 受体激动剂和阿昔洛韦。苄damine 、双氯芬酸/乙醚和长春新碱的局部给药 (离子导入) 同样与疗效无关，单独鞘内注射利多卡因或硬膜外注射利多卡因和甲泼尼龙也不相关, 静脉注射利多卡因，Cronassial 皮下注射，或针灸。然而，许多证明缺乏疗效的试验代表了相对较低数量的患者发作或单剂量研究, 因此，将此类干预视为 “尚未经过充分测试”，而不是证明 “没有疗效的证据”，可能是合适的。外用阿司匹林/乙醚尚未得到充分测试。结论: 证据基础支持在 PHN 中口服三环抗抑郁药、某些阿片类药物和加巴喷丁素。同样支持利多卡因贴剂和辣椒素的局部治疗。鞘内注射甲泼尼龙似乎与高疗效相关，但其安全性需要进一步评估。