ImportanceShort-term and long-term opioid treatment have been associated with increased pain sensitivity (ie, opioid-induced hyperalgesia). Treatment of opioid use disorder (OUD) mainly involves maintenance with methadone and buprenorphine, and observations of heightened cold pain sensitivity among patients are often considered evidence of opioid-induced hyperalgesia.ObjectiveTo critically examine the evidence that hyperalgesia in patients with OUD is related to opioid use.Data SourcesWeb of Science, PubMed, and Embase between March 1, 2023, and April 12, 2024, were searched.Study SelectionStudies assessing cold pressor test (CPT) pain responses during treatment seeking, pharmacological treatment, or abstinence in patients with OUD history were included.Data Extraction and SynthesisMultilevel random-effects models with robust variance estimation were used for all analyses. Study quality was rated with the JBI checklist. Funnel plots and Egger regression tests were used to assess reporting bias.Main Outcomes and MeasuresMain outcomes were pain threshold, tolerance, and intensity in patients and healthy controls, and unstandardized, standardized (Hedges g), and percentage differences (%Δ) in these measures between patients and controls. The association between pain sensitivity and opioid tolerance, withdrawal, and abstinence indices was tested with meta-regression.ResultsThirty-nine studies (1385 patients, 741 controls) met the inclusion criteria. Most studies reported CPT data on patients undergoing opioid agonist treatment. These patients had a mean 2- to 3-seconds lower pain threshold (95% CI, −4 to −1; t test P = .01; %Δ, −22%; g = −0.5) and 29-seconds lower pain tolerance (95% CI, −39 to −18; t test P < .001; %Δ, −52%; g = −0.9) than controls. Egger tests suggested that these differences may be overestimated. There were some concerns of bias due to inadequate sample matching and participant dropout. Meta-regressions yielded no clear support for hyperalgesia being opioid related.Conclusion and RelevancePatients receiving opioid agonist treatment for OUD are hypersensitive to cold pain. It remains unclear whether hyperalgesia develops prior to, independent of, or as a result of long-term opioid treatment. Regardless, future studies should investigate the impact of hyperalgesia on patients’ well-being and treatment outcomes.

中文翻译：

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有阿片类药物使用障碍病史的患者痛觉过敏


重要性短期和长期阿片类药物治疗与疼痛敏感性增加（即阿片类药物诱导的痛觉过敏）有关。阿片类药物使用障碍 （OUD） 的治疗主要包括使用美沙酮和丁丙诺啡维持治疗，观察到患者对冷痛敏感度升高通常被认为是阿片类药物诱导的痛觉过敏的证据。目的批判性地检查 OUD 患者痛觉过敏与阿片类药物使用有关的证据。数据源检索了 2023 年 3 月 1 日至 2024 年 4 月 12 日期间的 Web of Science、PubMed 和 Embase。研究选择包括评估有 OUD 病史的患者在寻求治疗、药物治疗或戒断期间的冷加压试验 （CPT） 疼痛反应的研究。资料提取和综合所有分析均采用具有稳健方差估计的多级随机效应模型。使用 JBI 检查表对研究质量进行评级。漏斗图和 Egger 回归检验用于评估报告偏倚。主要结局和指标主要结局是患者和健康对照者的疼痛阈值、耐受性和强度，以及患者和对照组之间这些指标的非标准化、标准化 （Hedges g） 和百分比差异 （%Δ）。通过荟萃回归测试疼痛敏感性与阿片类药物耐受性、戒断和戒断指数之间的关联。结果39 项研究 （1385 名患者，741 名对照） 符合纳入标准。大多数研究报告了接受阿片类激动剂治疗的患者的 CPT 数据。与对照组相比，这些患者的疼痛阈值平均低 2 至 3 秒 （95% CI， -4 至 -1;t 检验 P = .01;%Δ，-22%;g = -0.5） 和疼痛耐受性平均低 29 秒 （95% CI， -39 至 -18;t 检验 P < .001;%Δ， -52%;g = -0.9）。 Egger 检验表明，这些差异可能被高估了。由于样本匹配不充分和受试者退出，存在一些偏倚的担忧。Meta 回归分析没有明确支持痛觉过敏与阿片类药物相关。结论和相关性接受阿片类激动剂治疗的 OUD 患者对冷痛过敏。目前尚不清楚痛觉过敏是在长期阿片类药物治疗之前、独立于还是作为长期阿片类药物治疗的结果而发展。无论如何，未来的研究应该调查痛觉过敏对患者健康和治疗结果的影响。