Lack of effect of chronic dextromethorphan on experimental pain tolerance in methadone-maintained patients
Lack of effect of chronic dextromethorphan on experimental pain tolerance in methadone-maintained patients
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DOI：
10.1111/j.1369-1600.2008.00112.x
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发表时间：
2008-09-01
影响因子：
3.4
通讯作者：
Torrington, Matt A.
中科院分区：
文献类型：
--
作者：
Compton, Peggy A.;Ling, Walter;Torrington, Matt A.
有充分的证据表明，阿片类药物维持治疗成瘾（即美沙酮）的个体对实验性疼痛的耐受性低于匹配的对照组或前阿片类药物成瘾者，这一现象理论上反映了阿片类药物诱导的痛觉过敏（OIH）。背角神经元兴奋性嗜离子性n -甲基- d -天冬氨酸（NMDA）受体的激动剂活性与OIH的发展及其在临床水平上的阿片耐受性的推定表达有关。本研究的目的是评估nmda受体拮抗剂右美沙芬（DEX）在美沙酮维持（MM）患者中逆转或治疗OIH的潜在效用。利用临床试验设计和双盲条件，在一个特征明确的MM患者样本中，与安慰剂相比，在为期5周的DEX（滴定至480 mg/天）试验后，疼痛阈值和耐受性[冷压（CP）和电刺激（ES）]的变化进行了评估。样本（n = 40） 53%为男性，种族多样（拉丁裔53%，非裔28%，白人10%，其他9%），平均年龄48.0岁（SD = 6.97）。经t检验分析，两组患者用药前后CP疼痛阈值、CP疼痛耐受性、ES疼痛阈值或ES疼痛耐受性均无差异。值得注意的是，DEX相关的变化在性别上有显著差异，女性对DEX治疗的疼痛耐受性倾向于降低。这些结果支持慢性高剂量NMDA拮抗剂并不能改善MM患者的疼痛耐受性，尽管性别对DEX反应有影响。
Good evidence exists to suggest that individuals on opioid maintenance for the treatment of addiction (i.e. methadone) are less tolerant of experimental pain than are matched controls or ex-opioid addicts, a phenomenon theorized to reflect opioid-induced hyperalgesia (OIH). Agonist activity at the excitatory ionotropic N-methyl-D-aspartate (NMDA) receptor on dorsal horn neurons has been implicated in the development of both OIH and its putative expression at the clinical level-opioid tolerance. The aim of this study was to evaluate the potential utility of the NMDA-receptor antagonist, dextromethorphan (DEX), to reverse or treat OIH in methadone-maintenance (MM) patients. Utilizing a clinical trial design and double-blind conditions, changes in pain threshold and tolerance [cold pressor (CP) and electrical stimulation (ES)] following a 5-week trial of DEX (titrated to 480 mg/day) in comparison with placebo was evaluated in a well-characterized sample of MM patients. The sample (n = 40) was 53% male and ethnically diverse (53% Latino, 28% African American, 10% White, 9% other), with a mean age of 48.0 years (SD = 6.97). Based on t-test analyses, no difference was found between groups on CP pain threshold, CP pain tolerance, ES pain threshold or ES pain tolerance, both pre- and postmedication. Notably, DEX-related changes significantly differed by gender, with women tending to show diminished tolerance for pain with DEX therapy. These results support that chronic high-dose NMDA antagonism does not improve tolerance for pain in MM patients, although a gender effect on DEX response is suggested.