Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Basic Clin Pharmacol Toxicol. 2018 Dec;123(6):727-731. doi: 10.1111/bcpt.13078. Epub 2018 Jul 31.
Offset analgesia (OA) is a pain-modulating mechanism described as a disproportionately large decrease in pain intensity evoked by a discrete decrease in stimulus temperature. The role of the opioidergic, serotonergic and noradrenergic systems on OA remains unclear. The aim of this study was to evaluate whether OA is modulated by an opioid (oxycodone) and a serotonin and noradrenaline reuptake inhibitor (venlafaxine) in terms of psychophysical assessments. In this randomized, double-blinded, placebo-controlled cross-over study, 20 healthy male participants (mean age: 24.6 ± 2.5 years) received 10 mg oxycodone, 37.5 mg venlafaxine or placebo twice daily for 5 days in three periods. OA was induced by noxious thermal stimulation on the forearm at baseline and last day of treatment. A control session of constant stimulus intensity was included for comparison. OA magnitude was unaffected by oxycodone and venlafaxine (p = 0.20 and p = 0.90, respectively). Oxycodone affected the control paradigm where a decreased rating of pain intensity was observed compared to placebo (p = 0.001). OA could not be modulated by oxycodone or venlafaxine and may be a robust phenomenon in healthy volunteers and not suitable for exploring pharmacological mechanisms of analgesia in human beings.
偏移镇痛（OA）是一种疼痛调节机制，被描述为刺激温度离散下降时引起的疼痛强度不成比例的大幅下降。阿片类、5-羟色胺和去甲肾上腺素系统对 OA 的作用仍不清楚。本研究旨在评估 OA 是否可通过阿片类药物（羟考酮）和 5-羟色胺和去甲肾上腺素再摄取抑制剂（文拉法辛）进行调节，通过心理物理评估来评估。在这项随机、双盲、安慰剂对照的交叉研究中，20 名健康男性参与者（平均年龄：24.6 ± 2.5 岁）在三个时期内每天两次接受 10 毫克羟考酮、37.5 毫克文拉法辛或安慰剂治疗 5 天。在基线和治疗的最后一天，在前臂上进行有害热刺激以诱导 OA。包括一个恒定刺激强度的对照疗程进行比较。OA 幅度不受羟考酮和文拉法辛的影响（p = 0.20 和 p = 0.90）。与安慰剂相比，羟考酮影响了对照范式，观察到疼痛强度评分降低（p = 0.001）。OA 不能被羟考酮或文拉法辛调节，并且可能是健康志愿者中的一种稳健现象，不适合用于探索人类镇痛的药理学机制。
