Department of Anesthesiology and Critical Care, Division of Pulmonary and Critical Care, University of Pennsylvania, PA 19104, USA.
Clin J Pain. 2012 Nov-Dec;28(9):747-54. doi: 10.1097/AJP.0b013e3182442b1c.
The mechanism whereby acute postsurgical pain can persist and become chronic remains unknown. Thoracotomy is a common procedure with a high incidence of long-term pain for which acute postsurgical pain is an established risk factor. Therefore, the genetic basis of elevations in acute postsurgical pain after thoracotomy was investigated.
A cohort of thoracotomy patients participating in an ongoing trial of outcomes after cancer were enrolled. A standard combined general and epidural anesthetic and surgical approach were used. All patients received a standardized postoperative epidural analgesia regimen. Postoperatively, pain scores were determined and blood was collected for genotyping. Our a priori hypothesis was that variability of genes involved in nociception and analgesic therapy would predict pain score ≥3 of 10 on the third postoperative day.
Ninety patients with pain and genotyping data on postoperative day 3 were examined. We found no association between markers in COMT, COX1, COX2, and TRPV1 and postoperative pain. We demonstrated several statistically significant associations with 4 single nucleotide polymorphism markers in OPRM1 (odds ratio, 95% confidence intervals): rs634479 (0.4, 0.17, 0.97), rs499796 (0.35, 0.13, 0.92), rs548646 (0.47, 0.23, 0.97), and rs679987 (0.1, 0.01, 0.84). From these, we inferred 2 haplotype blocks in OPRM1 where both had a frequency of 9% and P=0.03 and 0.04. Previously published functional single nucleotide polymorphisms in OPRM1 and COMT were not associated with increased pain on the third postoperative day.
We identified previously unpublished haplotypes of the OPRM1 receptor that predicted increases in self-reported pain on the third postoperative day after thoracotomy. These findings require replication and further refinement before their impact on patient care can be determined.
急性术后疼痛持续存在并发展为慢性疼痛的机制尚不清楚。开胸术是一种常见的手术，其长期疼痛的发生率很高，而急性术后疼痛是其明确的危险因素。因此，本研究旨在探讨开胸术后急性术后疼痛升高的遗传基础。
本研究纳入了正在进行的癌症患者术后结局研究中的一组开胸术患者。采用标准的全身麻醉和硬膜外麻醉及手术方法。所有患者均接受标准化的术后硬膜外镇痛方案。术后，测定疼痛评分并采集血液进行基因分型。我们的先验假设是，参与痛觉和镇痛治疗的基因的变异性将预测术后第 3 天疼痛评分≥3/10。
对 90 例术后第 3 天有疼痛和基因分型数据的患者进行了检查。我们未发现 COMT、COX1、COX2 和 TRPV1 中的标志物与术后疼痛之间存在关联。我们在 OPRM1 中发现了 4 个单核苷酸多态性标记物与术后疼痛存在统计学显著关联（比值比，95%置信区间）：rs634479（0.4，0.17，0.97）、rs499796（0.35，0.13，0.92）、rs548646（0.47，0.23，0.97）和 rs679987（0.1，0.01，0.84）。由此推断出 OPRM1 中存在 2 个单倍型块，其频率均为 9%，P 值分别为 0.03 和 0.04。先前发表的 OPRM1 和 COMT 中的功能性单核苷酸多态性与术后第 3 天疼痛增加无关。
本研究发现了 OPRM1 受体的先前未发表的单倍型，这些单倍型可预测开胸术后第 3 天的自我报告疼痛增加。这些发现需要进一步复制和细化，然后才能确定其对患者护理的影响。
