Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
Br J Clin Pharmacol. 2010 Aug;70(2):189-200. doi: 10.1111/j.1365-2125.2010.03700.x.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Previous studies using short-lasting experimental pain stimulations in healthy volunteers have shown differences in opioid effects regarding visceral pain stimulations. However, these differences can be more pronounced in patients due to a sensitized pain system. Therefore, the aim of the present study was to mimic the clinical situation by investigating opioid effects on experimental pain in healthy volunteers after experimentally evoked hyperalgesia. WHAT THIS STUDY ADDS? * We now know that morphine and oxycodone exerts different effects in the sensitized pain system as we found a greater analgesic effect of oxycodone in response to skin, muscle and oesophageal pain stimulation. This supports clinicians' experiences that oxycodone can be superior to morphine in the treatment of some pain conditions. The evoked hyperalgesia bridged findings from studies in healthy volunteers to patients, and new fundamental knowledge on different analgesic effects in hyperalgesia was found. AIM Similar analgesics may have different analgesic potencies especially in patients in whom the pain system is sensitized. The aim was to investigate different opioid effects on experimental pain after the sensitized pain system was mimicked evoking hyperalgesia in healthy volunteers. METHODS Twenty-four healthy volunteers were randomized to treatment with morphine (30 mg orally) and oxycodone (15 mg orally) or placebo in a double-blind crossover study. Hyperalgesia was induced by oesophageal perfusion with acid and capsaicin. Several exploratory endpoints were studied using skin heat, muscle pressure and oesophageal mechanical, heat and electrical stimulation. Effects on pain from deeper structures were considered most important. RESULTS Different analgesic potencies were found. Oxycodone had a greater analgesic effect than morphine attenuating pain from: (i) heat stimulation of skin (P= 0.016); difference between the means of 0.39 degrees C, 95% CI 0.22, 2.09. (ii) muscle pressure (P < 0.001); difference between the means of 11.93kPa, 95% CI 5.4, 18.5. (iii) oesophageal heat stimulation (P < 0.001); difference between the means of 38.54 cm(2), 95% CI 15.37, 61.71 and (iv) oesophageal electrical stimulation (P= 0.016); difference between the means of 6.69mA, 95% CI 1.23, 12.13. CONCLUSION After sensitization of the pain system different analgesic potencies of morphine and oxycodone were found in response to skin, muscle and oesophageal pain stimulation, in which oxycodone had a greater effect. As similar differential analgesic potencies of the two opioids have been found in patients with chronic pain, the experimental hyperalgesia model bridged findings from studies in healthy volunteers to patients.
关于这个主题，已有以下几点是已知的：
先前使用健康志愿者进行的短暂性实验性疼痛刺激的研究表明，在涉及内脏疼痛刺激时，阿片类药物的作用存在差异。
然而，由于疼痛系统敏感化，这些差异在患者中可能更为明显。
因此，本研究的目的是通过在健康志愿者中模拟实验性诱发的痛觉过敏来研究阿片类药物对实验性疼痛的影响，从而模拟临床情况。
我们现在知道，吗啡和羟考酮在敏感化的疼痛系统中具有不同的作用，因为我们发现羟考酮对皮肤、肌肉和食管疼痛刺激的镇痛作用更大。
这支持了临床医生的经验，即羟考酮在治疗某些疼痛病症方面可能优于吗啡。
诱发的痛觉过敏将健康志愿者研究中的发现与患者联系起来，并发现了痛觉过敏中不同镇痛作用的新的基础知识。
类似的镇痛药在敏感化的疼痛系统中可能具有不同的镇痛效力，尤其是在患者中。
本研究的目的是在健康志愿者中模拟敏感化的疼痛系统，诱发痛觉过敏，以研究不同阿片类药物对实验性疼痛的影响。
24 名健康志愿者随机分为吗啡（30mg 口服）和羟考酮（15mg 口服）或安慰剂的双盲交叉研究组。
通过食管灌注酸和辣椒素来诱导痛觉过敏。
使用皮肤热、肌肉压力和食管机械、热和电刺激来研究几个探索性终点。
认为对深部结构的疼痛影响最重要。
发现了不同的镇痛效力。
羟考酮的镇痛作用大于吗啡，可减轻以下方面的疼痛：
（i）皮肤热刺激（P=0.016）；
（ii）肌肉压力（P<0.001）；
（iii）食管热刺激（P<0.001）；
（iv）食管电刺激（P=0.016）。
在疼痛系统敏感化后，发现吗啡和羟考酮对皮肤、肌肉和食管疼痛刺激的镇痛效力不同，羟考酮的作用更大。
由于在慢性疼痛患者中发现了这两种阿片类药物的类似差异镇痛效力，因此实验性痛觉过敏模型将健康志愿者研究中的发现与患者联系起来。
