Ward Jennifer, Grinstead Anthony, Kemp Amy, Kersten Paula, Schmid Annina B, Ridehalgh Colette
Kent Community Hospitals NHS Foundation Trust, Sevenoaks Hospital, Hospital Road, Sevenoaks, Kent, TN11 3PG, UK.
Sussex Community NHS Foundation Trust, Trust HQ Brighton General Hospital, Brighton, BN2 3EW, UK.
Drugs. 2024 Dec;84(12):1603-1636. doi: 10.1007/s40265-024-02085-6. Epub 2024 Oct 26.
Highly variable pain mechanisms in people with low back pain or spine-related leg pain might contribute to inefficacy of neuropathic pain medication. This meta-analysis aimed to determine how neuropathic pain is identified in clinical trials for people taking neuropathic pain medication for low back pain or spine-related leg pain and whether subgrouping based on the presence of neuropathic pain influences efficacy.
EMBASE, MEDLINE, Cochrane Central, CINAHL [EBSCO], APA PsycINFO, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry were searched from inception to 14 May, 2024. Randomized and crossover trials comparing first-line neuropathic pain medication for people with low back pain or spine-related leg pain to placebo or usual care were included. Two independent authors extracted data. Random-effects meta-analyses of all studies combined, and pre-planned subgroup meta-analyses based on the certainty of neuropathic pain (according to the neuropathic pain Special Interest Group [NeuPSIG] neuropathic pain grading criteria) were completed. Certainty of evidence was judged using the grading of recommendations assessment development and evaluation [GRADE] framework.
Twenty-seven included studies reported on 3619 participants. Overall, 33% of studies were judged unlikely to include people with neuropathic pain, 26% remained unclear. Only 41% identified people with possible, probable, or definite neuropathic pain. For pain, general analyses revealed only small effects at short term (mean difference [MD] - 9.30 [95% confidence interval [CI] - 13.71, - 4.88], I = 87%) and medium term (MD - 5.49 [95% CI - 7.24, - 3.74], I = 0%). Subgrouping at short term revealed studies including people with definite or probable neuropathic pain showed larger effects on pain (definite; MD - 16.65 [95% CI - 35.95, 2.65], I = 84%; probable; MD - 10.45 [95% CI - 14.79, - 6.12], I = 20%) than studies including people with possible (MD - 5.50 [95% CI - 20.52, 9.52], I = 78%), unlikely (MD - 6.67 [95% CI - 10.58, 2.76], I = 0%), or unclear neuropathic pain (MD - 8.93 [95% CI - 20.57, 2.71], I = 96%). Similarly, general analyses revealed negligible effects on disability at short term (MD - 3.35 [95% CI - 9.00, 2.29], I = 93%) and medium term (MD - 4.06 [95% CI - 5.63, - 2.48], I = 0%). Sub-grouping at short term revealed larger effects in studies including people with definite/probable neuropathic pain (MD - 9.25 [95% CI - 12.59, - 5.90], I = 2%) compared with those with possible/unclear/unlikely neuropathic pain (MD -1.57 [95% CI - 8.96, 5.82] I = 95%). Medium-term outcomes showed a similar trend, but were limited by low numbers of studies. Certainty of evidence was low to very low for all outcomes.
Most studies using neuropathic pain medication for low back pain or spine-related leg pain fail to adequately consider the presence of neuropathic pain. Meta-analyses suggest neuropathic pain medication may be most effective in people with low back pain or spine-related leg pain with a definite/probable neuropathic pain component. However, the low to very low certainty of evidence and poor identification of neuropathic pain in most studies prevent firm recommendations.
下背痛或脊柱相关腿痛患者的疼痛机制高度可变，这可能导致神经性疼痛药物治疗无效。本荟萃分析旨在确定在针对下背痛或脊柱相关腿痛患者服用神经性疼痛药物的临床试验中，神经性疼痛是如何被识别的，以及基于神经性疼痛的存在进行亚组划分是否会影响疗效。
检索了EMBASE、MEDLINE、Cochrane Central、CINAHL[EBSCO]、APA PsycINFO、ClinicalTrials.gov和世界卫生组织国际临床试验注册库，检索时间从创建至2024年5月14日。纳入了比较一线神经性疼痛药物与安慰剂或常规护理用于下背痛或脊柱相关腿痛患者的随机试验和交叉试验。两名独立作者提取数据。完成了所有研究合并的随机效应荟萃分析，以及基于神经性疼痛的确定性（根据神经性疼痛特殊兴趣小组[NeuPSIG]神经性疼痛分级标准）预先计划的亚组荟萃分析。使用推荐分级评估、制定与评价[GRADE]框架判断证据的确定性。
27项纳入研究报告了3619名参与者。总体而言，33%的研究被判定不太可能纳入神经性疼痛患者，26%的情况仍不明确。只有41%的研究识别出可能、很可能或肯定患有神经性疼痛的患者。对于疼痛，一般分析显示短期（平均差[MD] - 9.30[95%置信区间[CI] - 13.71， - 4.88]，I² = 87%）和中期（MD - 5.49[95%CI - 7.24， - 3.74]，I² = 0%）仅有小的效应。短期亚组分析显示，纳入肯定或很可能患有神经性疼痛患者的研究对疼痛的影响更大（肯定；MD - 16.65[95%CI - 35.95，2.65]，I² = 84%；很可能；MD - 10.45[95%CI - 14.79， - 6.12]，I² = 20%），高于纳入可能（MD - 5.50[95%CI - 20.52，9.52]，I² = 78%）、不太可能（MD - 6.67[95%CI - 10.58，2.76]，I² = 0%）或不明确患有神经性疼痛（MD - 8.93[95%CI - 20.57，2.71]，I² = 96%）患者的研究。同样，一般分析显示短期（MD - 3.35[95%CI - 9.00，2.29]，I² = 93%）和中期（MD - 4.06[95%CI - 5.63， - 2.48]，I² = 0%）对残疾的影响可忽略不计。短期亚组分析显示，纳入肯定/很可能患有神经性疼痛患者的研究（MD - 9.25[95%CI - 12.59， - 5.90]，I² = 2%）与纳入可能/不明确/不太可能患有神经性疼痛患者的研究（MD -1.57[95%CI - 8.96，5.82]，I² = 95%）相比，影响更大。中期结果显示出类似趋势，但受研究数量较少的限制。所有结局的证据确定性均为低至极低。
大多数使用神经性疼痛药物治疗下背痛或脊柱相关腿痛的研究未能充分考虑神经性疼痛的存在。荟萃分析表明，神经性疼痛药物可能对具有肯定/很可能神经性疼痛成分的下背痛或脊柱相关腿痛患者最有效。然而，证据确定性低至极低以及大多数研究中对神经性疼痛的识别不佳，使得无法给出确切建议。
