Analgesia from a peripherally active κ-opioid receptor agonist in patients with chronic pancreatitis
Analgesia from a peripherally active κ-opioid receptor agonist in patients with chronic pancreatitis
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DOI：
10.1016/s0304-3959(02)00259-2
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发表时间：
2003-01-01
期刊：
影响因子：
7.4
通讯作者：
Curry, R
中科院分区：
文献类型：
--
作者：
Eisenach, JC;Carpenter, R;Curry, R
临床前研究表明，内脏传入组成性表达K-阿片受体（KOR），并且有害的内脏刺激可以通过KOR激活在外周部位被抑制。为了测试这些观察结果与人类的相关性，我们以随机、双盲的方式将外周选择性KOR激动剂（ADL 10-0101）或安慰剂输注到6名患有慢性胰腺炎和持续腹痛的患者中，尽管μ阿片激动剂治疗。使用疼痛程度估计来评估疼痛，每个患者选择一个开放式量表，并与他们从1.6 cm（2）热电极应用于皮肤并加热至49 ℃持续5 s的疼痛评级进行比较。将疼痛评分标准化为100分，研究药物治疗前的疼痛评分为40 - 70分，并且在接受该治疗的两个个体中不受安慰剂输注的影响。相比之下，ADL 10-0101输注将疼痛评分从输注前的63 +/- 7.6（平均值+/- SE）降低至输注后4小时的23 +/- 15（相对于基线P < 0.05）。1例接受安慰剂的患者和1例接受ADL 10-0101的患者在研究期间发生轻度头痛。1例接受ADL 10-0101治疗的患者在4小时研究后站立时出现躁动，另1例出现无症状的一过性心律失常。两种治疗均不影响血压、心率、呼吸频率或血氧饱和度，研究期间无患者发生恶心。这些有限的数据支持这一假设，即人类内脏传入表达KOR和外周限制性KOR激动剂产生镇痛慢性内脏痛患者。(C)2002年国际疼痛研究协会。由Elsevier Science B. V.出版，版权所有。
Preclinical studies suggest that visceral afferents constitutively express K-opioid receptors (KORs) and that noxious visceral stimuli can be inhibited at a peripheral site by KOR activation. To test the relevance of these observations to humans, we infused, in a randomized, double blind manner, a peripherally selective KOR agonist (ADL 10-0101) or placebo into six patients with chronic pancreatitis and ongoing abdominal pain despite mu-opioid agonist therapy. Pain was assessed using a pain magnitude estimate, an open ended scale of each patient's choosing and compared to their rating of pain from a 1.6 cm(2) thermode applied to the skin and heated to 49degreesC for 5 s. Normalizing pain scores to this rating as 100, pain prior to study drug treatment was 40 70, and was unaffected by placebo infusion in the two individuals receiving this therapy. In contrast, ADL 10-0101 infusion reduced pain score from 63 +/- 7.6 (mean +/- SE) prior to infusion to 23 +/- 15 4 h after infusion (P < 0.05 vs. baseline). One patient receiving placebo and one receiving ADL 10-0101 experienced a mild headache during the study. One patient receiving ADL 10-0101 experienced restlessness and another had assymptomatic transient dysrhythmia upon standing after the 4 h study. Neither of the treatments affected blood pressure, heart rate, respiratory rate, or oxyhemoglobin saturation, and no patient experienced nausea during the study. These limited data support the hypothesis that human visceral afferents express KOR and that peripherally restricted KOR agonists produce analgesia in patients with chronic visceral pain. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.