Liu Jia, Wang Lu-Ning, McNicol Ewan D
Department of Neurology, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Beijing, China, 100053.
Cochrane Database Syst Rev. 2015 Apr 9;2015(4):CD009950. doi: 10.1002/14651858.CD009950.pub3.
Pain in Guillain-Barré syndrome (GBS) is common, yet it is often under recognised and poorly managed. In recent years, a variety of pharmacological treatment options have been investigated in clinical trials for people with GBS-associated pain. This is an updated version of the original Cochrane review published in Issue 10, 2013.
To assess the efficacy and safety of pharmacological treatments for various pain symptoms associated with GBS, during both the acute and convalescent (three months or more after onset) phases of GBS.
On 3 November 2014, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE. In addition, we searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform.
We included randomised controlled trials (RCTs) and quasi-RCTs in participants with confirmed GBS, with pain assessment as either the primary or secondary outcome. For cross-over trials, an adequate washout period between phases was required for inclusion.
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy and assessed the risk of bias of each study.
Three short-term RCTs, which enrolled 277 randomised participants with acute phase GBS, were included. Risk of bias in the included studies was generally unclear due to insufficient information. None of the included studies reported the primary outcome selected for this review, which was number of patients with self reported pain relief of 50% or greater. One small study investigated seven-day regimens of gabapentin versus placebo. Pain was rated on a scale from 0 (no pain) to 10 (maximum pain). Amongst the 18 participants, significantly lower mean pain scores were found at the endpoint (day 7) in the gabapentin phase compared to the endpoint of the placebo phase (mean difference -3.61, 95% CI -4.12 to -3.10) (very low quality evidence). For adverse events, no significant differences were found in the incidence of nausea (risk ratio (RR) 0.50, 95% CI 0.05 to 5.04) or constipation (RR 0.14, 95% CI 0.01 to 2.54). A second study enrolling 36 participants compared gabapentin, carbamazepine and placebo, all administered over seven days. Participants in the gabapentin group had significantly lower median pain scores on all treatment days in comparison to the placebo and carbamazepine groups (P < 0.05). There were no statistically significant differences in the median pain scores between the carbamazepine and placebo groups from day 1 to day 3, but from day 4 until the end of the study significantly lower median pain scores were noted in the carbamazepine group (P < 0.05) (very low quality evidence). There were no adverse effects of gabapentin or carbamazepine reported, other than sedation. One large RCT (223 participants, all also treated with intravenous immunoglobulin), compared a five-day course of methylprednisolone with placebo and found no statistically significant differences in number of participants developing pain (RR 0.89, 95% CI 0.68 to 1.16), number of participants with decreased pain (RR 0.95, 95% CI 0.63 to 1.42) or number of participants with increased pain (RR 0.85, 95% CI 0.52 to 1.41) (low quality evidence). The study did not report whether there were any adverse events.
AUTHORS' CONCLUSIONS: Since the last version of this review we found no new studies. While management of pain in GBS is essential and pharmacotherapy is widely accepted as being an important component of treatment, this review does not provide sufficient evidence to support the use of any pharmacological intervention in people with pain in GBS. Although reductions in pain severity were found when comparing gabapentin and carbamazepine with placebo, the evidence was limited and its quality very low. Larger, well-designed RCTs are required to further investigate the efficacy and safety of potential interventions for patients with pain in GBS. Additionally, interventions for pain in the convalescent phase of GBS should be investigated.
吉兰 - 巴雷综合征（GBS）患者中疼痛很常见，但往往未得到充分认识且管理不善。近年来，针对GBS相关疼痛患者，在临床试验中研究了多种药物治疗方案。这是2013年第10期发表的原始Cochrane系统评价的更新版本。
评估GBS急性期和恢复期（发病三个月或更长时间后）各种与GBS相关疼痛症状的药物治疗的疗效和安全性。
2014年11月3日，我们检索了Cochrane神经肌肉疾病小组专业注册库、Cochrane系统评价数据库、医学期刊数据库（MEDLINE）和荷兰医学文摘数据库（EMBASE）。此外，我们还检索了美国国立医学图书馆临床试验数据库（ClinicalTrials.gov）和世界卫生组织（WHO）国际临床试验注册平台。
我们纳入了确诊为GBS的参与者的随机对照试验（RCT）和半随机对照试验，将疼痛评估作为主要或次要结局。对于交叉试验，各阶段之间需要有足够的洗脱期才能纳入。
两位综述作者独立筛选已识别记录的标题和摘要，选择纳入的研究，提取合格数据，交叉核对数据准确性，并评估每项研究的偏倚风险。
纳入了三项短期RCT，共277名急性期GBS随机参与者。由于信息不足，纳入研究中的偏倚风险一般不明确。纳入的研究均未报告本次综述选定的主要结局，即自我报告疼痛缓解50%或更多的患者数量。一项小型研究比较了加巴喷丁与安慰剂的七日治疗方案。疼痛程度按0（无疼痛）至10（最大疼痛）评分。在18名参与者中，与安慰剂阶段的终点相比，加巴喷丁阶段终点（第7天）的平均疼痛评分显著更低（平均差值 -3.61，95%置信区间 -4.12至 -3.10）（极低质量证据）。对于不良事件，恶心发生率（风险比（RR）0.50，95%置信区间0.05至5.04）或便秘发生率（RR 0.14，95%置信区间0.01至2.54）均未发现显著差异。第二项纳入36名参与者的研究比较了加巴喷丁、卡马西平和安慰剂，均给药7天。与安慰剂组和卡马西平组相比，加巴喷丁组在所有治疗日的中位疼痛评分显著更低（P < 0.05）。从第1天到第3天，卡马西平组和安慰剂组的中位疼痛评分无统计学显著差异，但从第4天到研究结束，卡马西平组的中位疼痛评分显著更低（P < 0.05）（极低质量证据）。除镇静作用外，未报告加巴喷丁或卡马西平的其他不良反应。一项大型RCT（223名参与者，均同时接受静脉注射免疫球蛋白治疗）比较了为期五天的甲泼尼龙疗程与安慰剂，发现发生疼痛的参与者数量（RR 0.89，95%置信区间0.68至1.16）、疼痛减轻的参与者数量（RR 0.95，95%置信区间0.63至1.42）或疼痛加重的参与者数量（RR 0.85，95%置信区间0.52至1.41）均无统计学显著差异（低质量证据）。该研究未报告是否有任何不良事件。
自本综述的上一版本以来，我们未发现新的研究。虽然GBS疼痛管理至关重要，且药物治疗被广泛认为是治疗的重要组成部分，但本综述未提供足够证据支持对GBS疼痛患者使用任何药物干预。虽然将加巴喷丁和卡马西平与安慰剂比较时发现疼痛严重程度有所降低，但证据有限且质量极低。需要开展更大规模、设计良好的RCT，以进一步研究GBS疼痛患者潜在干预措施的疗效和安全性。此外，应研究GBS恢复期疼痛的干预措施。
