Department of Neurology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
Department of Biostatistics, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.
Eur J Cancer. 2018 Dec;105:79-87. doi: 10.1016/j.ejca.2018.09.036. Epub 2018 Nov 12.
To investigate whether clinical cancer patients with mixed nociceptive-neuropathic pain are less responsive to opioids than patients with nociceptive pain.
Pain is common in advanced cancer patients. Pain driven by neuropathic mechanisms is considered to be resistant to opioids. This hypothesis is mainly based on animal studies and single-dose opioid studies in humans but has not been confirmed in clinical practice.
Data were prospectively collected from 240 clinical cancer pain patients using opioids. Multiple linear regression was used for assessing the associations between the logarithm of the morphine equivalent dose (MED) at three days after admission (T = 3d) relative to admission (T = 0d) (logRMED) and type of pain (nociceptive versus mixed pain), corrected for gender, age, primary cancer site and use of non-opioid and adjuvant analgesics. As secondary outcome measures, associations between logMED and logPFent (fentanyl plasma level) at T = 3d and type of pain were assessed.
Pain intensity between T = 0d and T = 3d was significantly and evenly reduced in patients with nociceptive pain (n = 173) and mixed pain (n = 67). Median (interquartile range) MED was 20 (10-52) and 20 (20-80) mg (T = 0d), 40 (10-67) and 40 (20-100) mg (T = 3d), median PFent (T = 3d) was 1.59 (0.58-3.19) and 1.38 (0.54-4.39) ng/ml, none of them significantly different, in patients with nociceptive and mixed pain, respectively. Neither logRMED, logMED (T = 3d), or logPFent (T = 3d) was significantly associated with type of pain, after correction for confounding factors.
We conclude that, at least in clinical cancer patients, mixed pain is as responsive to opioids as nociceptive pain.
探讨癌症混合痛患者对阿片类药物的反应是否不如单纯痛患者。
疼痛在晚期癌症患者中很常见。由神经病理性机制引起的疼痛被认为对阿片类药物有抵抗力。这一假设主要基于动物研究和人体单次阿片类药物研究，但尚未在临床实践中得到证实。
前瞻性收集 240 例使用阿片类药物的临床癌痛患者的数据。采用多元线性回归分析评估入院后第 3 天（T=3d）与入院时（T=0d）的吗啡等效剂量（MED）的对数值（logRMED）与疼痛类型（躯体痛与混合痛）之间的关系，并校正性别、年龄、原发癌部位和非阿片类药物及辅助镇痛药的使用情况。作为次要观察指标，评估 logMED 与 T=3d 时的 logPFent（芬太尼血浆浓度）与疼痛类型之间的关系。
躯体痛患者（n=173）和混合痛患者（n=67）的疼痛强度在 T=0d 至 T=3d 期间均显著且均匀地降低。中位（四分位间距）MED 分别为 20（10-52）和 20（20-80）mg（T=0d）、40（10-67）和 40（20-100）mg（T=3d）；中位 PFent（T=3d）分别为 1.59（0.58-3.19）和 1.38（0.54-4.39）ng/ml，在躯体痛和混合痛患者中均无显著差异。校正混杂因素后，logRMED、logMED（T=3d）和 logPFent（T=3d）均与疼痛类型无显著相关性。
我们的结论是，至少在临床癌症患者中，混合痛对阿片类药物的反应与躯体痛一样。
