Randomized clinical trial: inhibition of the TRPV1 system in patients with nonerosive gastroesophageal reflux disease and a partial response to PPI treatment is not associated with analgesia to esophageal experimental pain
Randomized clinical trial: inhibition of the TRPV1 system in patients with nonerosive gastroesophageal reflux disease and a partial response to PPI treatment is not associated with analgesia to esophageal experimental pain
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DOI：
10.3109/00365521.2012.758769
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发表时间：
2013-03-01
影响因子：
1.9
通讯作者：
Drewes, Asbjorn Mohr
中科院分区：
文献类型：
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作者：
Krarup, Anne Lund;Ny, Lars;Drewes, Asbjorn Mohr
目标。许多非糜烂性反流病(NERD)患者对质子泵抑制剂(PPI)的缓解不足。一些患者有食道过敏症，可能对瞬时受体电位香草素1(TRPV1)拮抗剂有反应。瞄准。目的：探讨TRPV1拮抗剂AZD1386对NERD患者实验性食管痛的影响。材料和方法。入选的患者在入选前有NERD和部分PPI反应(中到重度胃灼热或反流，尽管PPI治疗=6周，但仍为每周3天)。14名患者(21-69岁，9名女性)被随机分组进入这项安慰剂对照、双盲、交叉研究，检查单剂量(95毫克)AZD1386的疗效。在治疗日，每个参与者的食道都会在丹麦和瑞典的教学医院用热、膨胀和电流刺激。热痛和压痛作为躯体控制刺激。按方案对结果进行分析。结果。在14名随机患者中，12名患者接受了AZD1386治疗。AZD1386对热[-3%，95%可信区间(-22；20%)]、扩张(-11%，95%可信区间，-28；10%)或电流(6%，95%可信区间，-10；25%)的中度痛阈值没有显著影响。平均皮肤耐热性提高了4.9摄氏度(95%可信区间，3.7；6.2摄氏度)。AZD1386使最高体温平均升高0.59摄氏度(95%CI，0.40-0.79摄氏度)，并在4小时内恢复正常。AZD1386对NERD患者的实验性食管痛无镇痛作用，部分PPI反应，但可提高皮肤耐热性。在这些患者中，TRPV1在热、机械和电引起的食管痛中不起主要作用。ClinicalTrials.gov标识符：D9127C00002。
Objective. Many patients with nonerosive reflux disease (NERD) have insufficient relief on proton pump inhibitors (PPIs). Some patients have a hypersensitive esophagus and may respond to transient receptor potential vanilloid 1 (TRPV1) antagonists. Aim. To investigate the effect of the TRPV1 antagonist AZD1386 on experimental esophageal pain in NERD patients. Material and methods. Enrolled patients had NERD and a partial PPI response (moderate-to-severe heartburn or regurgitation >= 3 days/week before enrolment despite >= 6 weeks' PPI therapy). Fourteen patients (21-69 years, 9 women) were block-randomized into this placebo-controlled, double-blinded, crossover study examining efficacy of a single dose (95 mg) of AZD1386. On treatment days, each participant's esophagus was stimulated with heat, distension, and electrical current at teaching hospitals in Denmark and Sweden. Heat and pressure pain served as somatic control stimuli. Per protocol results were analyzed. Results. Of 14 randomized patients, 12 were treated with AZD1386. In the esophagus AZD1386 did not significantly change the moderate pain threshold for heat [-3%, 95% confidence interval (CI), -22;20%], distension (-11%, 95% CI, -28;10%), or electrical current (6%, 95% CI, -10;25%). Mean cutaneous heat tolerance increased by 4.9 degrees C (95% CI, 3.7;6.2 degrees C). AZD1386 increased the maximum body temperature by a mean of 0.59 degrees C (95% CI, 0.40-0.79 degrees C), normalizing within 4 h. Conclusions. AZD1386 had no analgesic effect on experimental esophageal pain in patients with NERD and a partial PPI response, whereas it increased cutaneous heat tolerance. TRPV1 does not play a major role in heat-, mechanically and electrically evoked esophageal pain in these patients. ClinicalTrials.gov identifier: D9127C00002.