VA Connecticut Healthcare System, West Haven, Connecticut, USA.
Yale University School of Medicine, New Haven, Connecticut, USA.
Br J Clin Pharmacol. 2024 Dec;90(12):2977-2984. doi: 10.1111/bcp.16027. Epub 2024 Mar 4.
Despite a strong theoretical link between opioid craving and pain, little is known about the temporal relationship between pain and craving and the acute experience of pain in the context of methadone treatment. Using a cross-over design, the current study evaluated the time course of pain and craving and objective experience of pain as a function of the last methadone dose.
Participants (n = 20) presented for the study in the morning and either received methadone dose as scheduled or delayed dose until the afternoon. During the 4-h study visit, participants completed a series of tasks, including repeated assessment of pain and craving at 0, +40, +70, +130, +160 and +240 min and a cold pressor test (CPT) at +15 and +220 min.
Separate mixed model results demonstrated no effect of dosing condition on craving; however, there was a significant dosing condition by time interaction (F(5,209) = 3.38, P = .006) such that pain increased over time in the delayed methadone condition but decreased in time in the scheduled methadone condition. A mixed model predicting self-reported pain revealed a three-way interaction between dosing condition, craving and time (F(5,197) = 2.39, P = .039) explained by a positive association between craving and pain at each time point (except 240 min) in delayed condition (P-range = .004-.0001). A separate mixed model on CPT data indicated a significant condition by time interaction such that pain threshold decreased in the delayed, but not scheduled, condition (F(1,57) = 4.01, P = .050).
These preliminary findings highlight the potential for increased risks after even a short delay in receiving a methadone dose.
尽管阿片类药物渴求与疼痛之间存在很强的理论联系,但对于疼痛与渴求之间的时间关系以及美沙酮治疗背景下急性疼痛的体验知之甚少。本研究采用交叉设计,评估了疼痛和渴求的时间进程以及作为最后一次美沙酮剂量函数的疼痛的客观体验。
参与者(n=20)在上午到研究现场就诊,要么按计划接受美沙酮剂量,要么将剂量推迟到下午。在 4 小时的研究访问期间,参与者完成了一系列任务,包括在 0、+40、+70、+130、+160 和+240 分钟时重复评估疼痛和渴求,以及在+15 和+220 分钟时进行冷加压测试(CPT)。
单独的混合模型结果表明,给药条件对渴求没有影响;然而,存在一个显著的给药条件与时间的交互作用(F(5,209)=3.38,P=0.006),即延迟美沙酮条件下疼痛随时间增加,而在预定美沙酮条件下疼痛随时间减少。一个预测自我报告疼痛的混合模型显示,给药条件、渴求和时间之间存在三向交互作用(F(5,197)=2.39,P=0.039),这是由延迟条件下每个时间点(240 分钟除外)之间渴求与疼痛之间的正相关关系解释的(P 范围=0.004-0.0001)。对 CPT 数据的单独混合模型表明,条件与时间的交互作用显著,即疼痛阈值在延迟条件下下降,但在预定条件下没有下降(F(1,57)=4.01,P=0.050)。
这些初步发现强调了即使在延迟接受美沙酮剂量后,风险也可能增加。