Luo Yujia, Yang Yating, Schneider Carl, Balle Thomas
Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Brain and Mind Centre, The University of Sydney, 94 Mallet Street, Camperdown, NSW 2050, Australia.
Pharmaceuticals (Basel). 2023 Nov 30;16(12):1665. doi: 10.3390/ph16121665.
Pain can have a serious impact on a patient's physical, mental, and social health, often causing their quality of life to decline. Various nicotine dosage forms, such as nicotine patches and nasal spray, have been developed and used as analgesics in clinical settings. However, there is controversy over the anti-nociceptive effects of nicotine among different clinical trials. The purpose of this meta-analysis is to quantify the analgesic effect of nicotine patches, nicotine nasal spray, and tobacco smoking on pain in humans.
Relevant articles published in English prior to July 2023 were identified using the PubMed, Cochrane Library, and Embase online databases in accordance with PRISMA (2020) guidelines. Two reviewers independently screened and selected studies, extracted data, and assessed the quality of the included studies using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). RStudio was used for data synthesis, heterogeneity assessment, sensitivity analysis, publication bias assessment, trim-and-fill analyses, and generating forest plots.
Sixteen eligible articles, including k = 5 studies of pain tolerance ( = 210), k = 5 studies of pain threshold ( = 210), and k = 12 studies of pain scores (N = 1249), were included for meta-analysis. Meta-analytic integration for pain threshold (Hedges' g = 0.28, 95% CI = 0-0.55, Z = 1.99, = 0.05) and pain tolerance (Hedges' g = 0.32, 95% CI = 0.05-0.59, Z = 2.30, = 0.02) revealed that nicotine administered via tobacco smoke generated acute analgesic effects to thermal stimuli. Meta-analytic integration for pain scores revealed that nicotine had a weak anti-nociceptive effect on postoperative pain of -0.37 (95% CI = -0.77 to 0.03, Z = -1.80) but with no statistical significance ( = 0.07). In addition, a limited number of included studies revealed that long-term smoking produced hyperalgesia that may be characterized as small to medium in magnitude (Hedges' g = 0.37, 95% CI = 0.29-0.64, Z = 5.33, < 0.01).
These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine.
疼痛会对患者的身体、心理和社会健康产生严重影响，常常导致其生活质量下降。多种尼古丁剂型，如尼古丁贴片和鼻喷雾剂，已被研发并在临床环境中用作镇痛药。然而，不同临床试验中关于尼古丁的抗伤害感受作用存在争议。本荟萃分析的目的是量化尼古丁贴片、尼古丁鼻喷雾剂和吸烟对人类疼痛的镇痛效果。
根据PRISMA（2020）指南，使用PubMed、Cochrane图书馆和Embase在线数据库识别2023年7月之前发表的英文相关文章。两名 reviewers 独立筛选和选择研究、提取数据，并使用Cochrane随机试验偏倚风险工具（RoB 2）第2版评估纳入研究的质量。使用RStudio进行数据合成、异质性评估、敏感性分析、发表偏倚评估、修剪填充分析以及生成森林图。
纳入16篇符合条件的文章进行荟萃分析，其中k = 5项疼痛耐受性研究（n = 210），k = 5项疼痛阈值研究（n = 210），k = 12项疼痛评分研究（N = 1249）。疼痛阈值（Hedges' g = 0.28，95% CI = 0 - 0.55，Z = 1.99，P = 0.05）和疼痛耐受性（Hedges' g = 0.32，95% CI = 0.05 - 0.59，Z = 2.30，P = 0.02）的荟萃分析整合显示，通过吸烟给予尼古丁对热刺激产生急性镇痛作用。疼痛评分的荟萃分析整合显示，尼古丁对术后疼痛的抗伤害感受作用较弱，为 -0.37（95% CI = -0.77至0.03，Z = -1.80），但无统计学意义（P = 0.07）。此外，少数纳入研究显示，长期吸烟会产生痛觉过敏，其程度可能为轻度至中度（Hedges' g = 0.37，95% CI = 0.29 - 0.64，Z = 5.33，P < 0.01）。
这些结果有助于阐明试验的混合结果，并最终可能为疼痛治疗提供参考。我们观察到，急性给予尼古丁可延长实验室诱导的疼痛阈值和耐受时间，并可能轻度缓解术后疼痛。此外，长期吸烟可能对不同类型的慢性疼痛有伤害感受作用。需要更多研究来确定尼古丁在人类中的抗伤害感受作用，并了解尼古丁的最佳给药时机、剂量和方式。
