Pain Unit, Department of Health of Alicante.
Neuropharmacology on Pain (NED) Group, Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation).
Clin J Pain. 2020 Jun;36(6):420-429. doi: 10.1097/AJP.0000000000000824.
The use of opioids to relieve pain is a challenge because of the high variability in dose requirements and tolerance profiles. Among potential modulators are the individual's genetic background and being female. Our aim was to evaluate sex bias and genotype-related influence on opioid titration safety, in chronic low back pain (CLBP), the most frequent chronic noncancer pain.
A 3-year prospective study was developed in opioid-naive CLBP patients. Data were self-reported by patients (pain [Visual Analogy Scale], adverse events [AEs], and health care resource utilization) and physicians (analgesic prescription, morphine equivalent daily dose, and suspected adverse drug reactions [ADRs]). Outcomes were analyzed as patients with AEs (case) or without (control) together with patients' sex and genotype. Gene variants in OPRM1 (rs1799971), COMT (rs4680), ABCB1 (rs1045642), UGT2B7 (rs12233719 and rs7438135), KCNJ6 (rs2070995 and rs6517442), and CYP3A5*3 (rs776746) were assessed. The hospital ethics committee approved the study, and statistical analyses were performed with R, v.3.2.4.
A total of 179 patients were included (64% female, mean pain intensity 73±16 mm), and 90% of them presented at least 1 AE (median of 3 (1 to 6) AEs/patient) with a rate of 5 AEs: 1 ADR without differences due to sex. However, there is a significant delay in referral of female patients (a mean of 6 years) to the Pain Unit, being significantly 3 to 5 times more likely to present sleep or psychiatric disorders. Meanwhile male individuals showed more sexual and reproductive system disorders. Genotypes influenced skin (COMT, G472A-GG) and gastrointestinal (ABCB1, C3435T-CC) related problems.
Sex bias affects female patients resulting in a CLBP diagnostic delay and a different analgesic safety profile. Moreover, the individual's genetic background might be useful to predict certain AEs in opioid-naive patients under an opioid titration procedure. Addressing sex in necessary to resolve inequalities in health care access.
由于剂量需求和耐受谱的高度变异性，使用阿片类药物缓解疼痛是一个挑战。潜在的调节剂包括个体的遗传背景和女性。我们的目的是评估性别偏见和基因型相关因素对慢性低背痛（CLBP）中阿片类药物滴定安全性的影响，慢性低背痛是最常见的慢性非癌性疼痛。
对阿片类药物初治的 CLBP 患者进行了为期 3 年的前瞻性研究。数据由患者（疼痛[视觉类比量表]、不良反应[AE]和医疗保健资源利用）和医生（镇痛处方、吗啡等效日剂量和疑似药物不良反应[ADR]）自行报告。将有 AE（病例）和无 AE（对照）的患者与患者的性别和基因型一起进行分析。评估了 OPRM1（rs1799971）、COMT（rs4680）、ABCB1（rs1045642）、UGT2B7（rs12233719 和 rs7438135）、KCNJ6（rs2070995 和 rs6517442）和 CYP3A5*3（rs776746）的基因变异。医院伦理委员会批准了该研究，使用 R 软件（v3.2.4）进行统计分析。
共纳入 179 例患者（64%为女性，平均疼痛强度为 73±16mm），其中 90%至少出现 1 例 AE（中位数为 3（1 至 6）例 AE/患者），5 例 AE 发生率为 1 例 ADR，无性别差异。然而，女性患者到疼痛科就诊的时间明显延迟（平均延迟 6 年），出现睡眠或精神障碍的可能性显著增加 3 至 5 倍。与此同时，男性患者表现出更多的性功能和生殖系统障碍。基因型影响皮肤（COMT，G472A-GG）和胃肠道（ABCB1，C3435T-CC）相关问题。
性别偏见会影响女性患者，导致 CLBP 诊断延迟和不同的镇痛安全性特征。此外，个体的遗传背景可能有助于预测阿片类药物滴定过程中阿片类药物初治患者的某些 AE。解决性别问题对于解决医疗保健获取方面的不平等至关重要。
