Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Br J Clin Pharmacol. 2022 Dec;88(12):5307-5316. doi: 10.1111/bcp.15453. Epub 2022 Jul 20.
The aim of this study was to investigate the effects of tapentadol and oxycodone using the nociceptive withdrawal reflex and sensory evoked potentials.
Twenty-one healthy volunteers completed a cross-over trial with oxycodone (10 mg), tapentadol (50 mg) extended-release tablets, or placebo treatment administered orally BID for 14 days. Electrical stimulations were delivered on the plantar side of the foot to evoke a nociceptive withdrawal reflex at baseline and post-interventions. Electromyography, recorded at tibialis anterior, and electroencephalography were recorded for analysis of: number of reflexes, latencies, and area under the curve of the nociceptive withdrawal reflex as well as latencies, amplitudes and dipole sources of the sensory-evoked potential.
Tapentadol decreased the odds ratio of eliciting nociceptive withdrawal reflex by -0.89 (P = .001, 95% confidence interval [CI] -1.46, -0.32), whereas oxycodone increased the latency of the N1 component of the sensory-evoked potential at the vertex by 12.5 ms (P = .003, 95% CI 3.35, 21.69). Dipole sources revealed that the anterior cingulate component moved caudally for all three interventions (all P < .02), and the insula components moved caudally in both the oxycodone and tapentadol arms (all P < .03).
A decrease in the number of nociceptive withdrawal reflex was observed during tapentadol treatment, possibly relating to the noradrenaline reuptake inhibition effects on the spinal cord. Both oxycodone and tapentadol affected cortical measures possible due to μ-opioid receptor agonistic effects evident in the dipole sources, with the strongest effect being mediated by oxycodone. These findings could support the dual effect analgesic mechanisms of tapentadol in humans as previously shown in preclinical studies.
本研究旨在通过伤害性退缩反射和感觉诱发电位来探讨曲马多和羟考酮的作用。
21 名健康志愿者完成了一项交叉试验，分别接受羟考酮（10mg）、曲马多（50mg）控释片或安慰剂治疗，每日 2 次，共 14 天。在足底给予电刺激以诱发出伤害性退缩反射，在基线和干预后进行记录。肌电图记录于胫骨前肌，脑电图记录用于分析伤害性退缩反射的反射次数、潜伏期和曲线下面积以及感觉诱发电位的潜伏期、振幅和偶极子源。
曲马多使诱发出伤害性退缩反射的比值比降低了 0.89（P=0.001，95%置信区间 [CI] -1.46，-0.32），而羟考酮使顶点的感觉诱发电位 N1 成分的潜伏期增加了 12.5ms（P=0.003，95%CI 3.35，21.69）。偶极子源显示，所有三种干预措施的前扣带回成分都向尾侧移动（均 P<0.02），而在羟考酮和曲马多组中，岛叶成分都向尾侧移动（均 P<0.03）。
曲马多治疗时观察到伤害性退缩反射次数减少，可能与脊髓的去甲肾上腺素再摄取抑制作用有关。羟考酮和曲马多均影响皮质测量，可能与偶极子源中明显的μ-阿片受体激动作用有关，其中最强的作用是由羟考酮介导的。这些发现可以支持曲马多在人类中的双重作用镇痛机制，正如以前在临床前研究中所显示的那样。
