The use of opioids to relieve pain is a challenge because of the high variability in dose requirements and tolerance profiles. Amongst potential modulators are individual’s genetic background as well as being female. Our aim was to evaluate gender bias and genotype-related influence on opioid titration safety, in chronic low back pain (CLBP), as the most frequent chronic non-cancer pain.
A 3 years, prospective study, was developed in opioids naïve CLBP patients. Data was self-reported by patients (pain [Visual Analogy Scale, VAS], adverse events [AEs], and healthcare resources utilization) and physicians (analgesic prescription, morphine equivalent daily dose [MEDD] and suspected adverse drug reactions [ADRs]). Outcomes were analyzed as patients with AEs (case) or without (control) together with patients’ gender 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. 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 one AE (median of 3 (1-6) AEs/patient) with a rate of 5 AEs: 1 ADR without differences due to gender. However, there is a significant delay in referral of female patients (a mean of six years) to Pain Unit, being significantly 3 to 5 more likely to present sleep or psychiatric disorders. Meanwhile males showed more sexual and reproductive system disorders. Genotypes influenced skin (COMT, G472A-GG) and gastrointestinal (ABCB1, C3435T-CC) related problems.
A gender bias was evidenced due to a female delay in CLBP diagnostic and therapeutic with a different analgesic drug safety profile. Even more, individual’s genetic background might be useful to predict certain adverse events in opioid naïve patients under an opioid titration procedure. Addressing gender in necessary to resolve inequalities in health care access.