Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis.

The Neuropathic Pain Special Interest Group aimed to update treatment recommendations, published in 2015, on the basis of new evidence from randomised controlled trials, emerging neuromodulation techniques, and advances in evidence synthesis.

神经病理性疼痛特别兴趣小组旨在根据2015年以来随机对照试验的新证据、新兴的神经调制技术以及证据合成的进展，更新治疗建议。

Methods

For this systematic reviewand meta-analysis, we searched Embase, PubMed, the International Clinical Trials Registry, and ClinicalTrials.gov from data inception for neuromodulation trials and from Jan 1, 2013, for pharmacological interventions until Feb 12, 2024.

在本系统评价和荟萃分析中，我们从数据开始就对Embase、PubMed、国际临床试验注册处和ClinicalTrials.gov进行了检索，以寻找神经调控试验，并从2013年1月1日起对药物干预进行检索，直到2024年2月12日。

We included double-blind, randomised, placebo-controlledtrials that evaluated pharmacological and neuromodulation treatments administered for at least 3 weeks, or if there was at least 3 weeks of follow-up, and which included at least ten participants per group.

我们纳入了双盲、随机、安慰剂对照试验，这些试验评估了至少3周的药物和神经调控治疗，或者至少有3周的随访，并且每组至少有十名参与者。

Trials included participants of any age with neuropathic pain, defined by the International Association for the Study of Pain.

试验纳入了任何年龄的神经病理性疼痛患者，根据国际疼痛研究协会的定义。

We excluded trials with enriched enrolment randomised withdrawal designs and those with participants with mixed aetiologies (ie, neuropathic and non-neuropathic pain) and conditions such as complex regional pain syndrome, low back pain without radicular pain, fibromyalgia, and idiopathic orofacial pain.

我们排除了采用富集入组随机撤退设计的试验，以及那些包含混合病因（即神经病理性疼痛和非神经病理性疼痛）和复杂区域性疼痛综合征、无根性腰痛、纤维肌痛以及特发性口腔面痛等状况的患者。

We extracted summary data in duplicate from published reports, with discrepancies reconciled by a third independent reviewer on the platform Covidence.

我们从已发表的报告中成对提取了摘要数据，通过在Covidence平台上由第三位独立审查员解决差异。

The primary efficacy outcome was the proportion of responders (50% or 30% reduction in baseline pain intensity or moderate pain relief).

主要疗效结果是反应者的比例（基线疼痛强度降低50%或30%或中度疼痛缓解）。

The primary safety outcome was the number of participants who withdrew from the treatment owing to adverse events.

主要安全性结果是因不良事件退出治疗的参与者数量。

We calculated a risk difference for each comparison and did a random-effects meta-analysis.

我们为每次比较计算了风险差异，并进行了随机效应的荟萃分析。

Risk differences were used to calculate the number needed to treat (NNT) and the number needed to harm (NNH) for each treatment.

使用风险差异来计算每种治疗的治疗人数（NNT）和伤害人数（NNH）

Risk of bias was assessed by use of the Cochrane risk of bias tool 2 and certainty of evidence assessed by use of GRADE.

通过使用Cochrane偏倚风险工具2评估偏倚风险，通过使用GRADE评估证据的确定性

Recommendations were based on evidence of efficacy, adverse events, accessibility, and cost, and feedback from engaged lived experience partners.

建议基于疗效证据、不良事件、可及性和成本，以及来自参与的生活体验伙伴的反馈。

This study is registered on PROSPERO, CRD42023389375.

该研究已在PROSPERO上注册，注册号为CRD42023389375。

Results

We identified 313 trials (284 pharmacological and 29 neuromodulation studies) for inclusion in the meta-analysis.

我们确定了313项试验（284项药物学研究和29项神经调节研究）纳入荟萃分析。

Across all studies, 48 789 adult participants were randomly assigned to trial groups (20 611 female and 25 078 male participants, where sex was reported).

在所有研究中，共有48,789名成年参与者被随机分配到试验组（性别报告的有20,611名女性和25,078名男性参与者）。

Estimates for the primary efficacy and safety outcomes were tricyclic antidepressants (TCAs) NNT=4·6 (95% CI 3·2-7·7), NNH=17·1 (11·4-33·6; moderate certainty of evidence), α2δ-ligands NNT=8·9 (7·4-11·10), NNH=26·2 (20·4-36·5; moderate certainty of evidence), serotonin and norepinephrine reuptake inhibitors (SNRIs) NNT=7·4 (5·6-10·9), NNH=13·9 (10·9-19·0; moderate certainty of evidence), botulinum toxin (BTX-A) NNT=2·7 (1·8-9·61), NNH=216·3 (23·5-∞; moderate certainty of evidence), capsaicin 8% patches NNT=13·2 (7·6-50·8), NNH=1129·3 (135·7-∞; moderate certainty of evidence), opioids NNT=5·9 (4·1-10·7), NNH=15·4 (10·8-24·0; low certainty of evidence), repetitive transcranial magnetic stimulation (rTMS) NNT=4·2 (2·3-28·3), NNH=651·6 (34·7-∞; low certainty of evidence), capsaicin cream NNT=6·1 (3·1-∞), NNH=18·6 (10·6-77·1; very low certainty of evidence), lidocaine 5% plasters NNT=14·5 (7·8-108·2), NNH=178·0 (23·9-∞; very low certainty of evidence).

主要疗效和安全性的估计结果为：三环类抗抑郁药（TCAs）NNT=4.6（95% CI 3.2-7.7），NNH=17.1（11.4-33.6；中等证据确定性），α2δ-配体NNT=8.9（7.4-11.10），NNH=26.2（20.4-36.5；中等证据确定性），血清素和去甲肾上腺素再摄取抑制剂（SNRIs）NNT=7.4（5.6-10.9），NNH=13.9（10.9-19.0；中等证据确定性），肉毒杆菌毒素（BTX-A）NNT=2.7（1.8-9.61），NNH=216.3（23.5-∞；中等证据确定性），辣椒素8%贴片NNT=13.2（7.6-50.8），NNH=1129.3（135.7-∞；中等证据确定性），阿片类药物NNT=5.9（4.1-10.7），NNH=15.4（10.8-24.0；低证据确定性），重复经颅磁刺激（rTMS）NNT=4.2（2.3-28.3），NNH=651.6（34.7-∞；低证据确定性），辣椒素膏NNT=6.1（3.1-∞），NNH=18.6（10.6-77.1；非常低的证据确定性），利多卡因5%贴膏NNT=14.5（7.8-108.2），NNH=178.0（23.9-∞；非常低的证据确定性）。

The findings provided the basis for a strong recommendation for use of TCAs, α2δ-ligands, and SNRIs as first-line treatments; a weak recommendation for capsaicin 8% patches, capsaicin cream, and lidocaine 5% plasters as second-line recommendation; and a weak recommendation for BTX-A, rTMS, and opioids as third-line treatments for neuropathic pain.

这些发现为将TCAs、α2δ-配体和SNRIs作为一线治疗的强烈推荐提供了依据；对于辣椒素8%贴片、辣椒素膏和利多卡因5%贴膏作为二线推荐的弱推荐；以及对于BTX-A、rTMS和阿片类药物作为神经性疼痛的三线治疗的弱推荐。

interpretation

Our results support a revision of the Neuropathic Pain Special Interest Group recommendations for the treatment of neuropathic pain.

我们的研究结果支持对神经病理性疼痛特别兴趣小组（Neuropathic Pain Special Interest Group）治疗建议的修订。

Treatment outcomes are modest and for some treatments uncertainty remains.

治疗结果尚可，但对某些治疗方法仍存在不确定性。

Further large placebo-controlledor sham-controlled trials done over clinically relevant timeframes are needed.

需要进行更大规模的安慰剂对照或假手术对照试验，以覆盖临床相关的时间范围。

funding

NeuPSIG and ERA-NET Neuron.

NeuPSIG 和 ERA-NET Neuron。