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Genetic variants of oxytocin receptor gene (OXTR), morphine use, acute and persistent pain after cesarean delivery
Abstract Number: GM 4
Abstract Type: Original Research
It has recently been proposed that endogenous secretion of oxytocin during delivery and postpartum confers specific protection and explains the relatively low incidence of chronic pain after cesarean delivery compared with that occurring after other surgical procedures (1). To date, one study has reported the association of ABCB1 gene C3435T polymorphism and persistent pain after cesarean delivery (2). The aim of this study was to evaluate the effect of 3 SNPs previously identified on exon 3 of OXTR (3) on morphine use, acute and persistent pain after cesarean delivery.
This is a secondary analysis on a previously studied cohort of 620 women undergoing an elective cesarean delivery with a standardized spinal anesthetic (with 0.1mg morphine) (2). Post-operative pain was rescued with morphine iv PCA. Pain scores (VRPS 0-10) and nausea scores (0-10) were evaluated q4 for 24h. Persistent post-cesarean pain was evaluated by phone interview at 6 months. DNA isolated from venous blood was used, and exon 3 of OXTR was amplified by PCR and sequenced (Sanger method). Genetic variants and clinical outcomes were analyzed using one way ANOVA (SYSTAT 13, Chicago, IL, USA).
The occurrence of 3 SNPs on exon 3 (rs2228485 C/T, rs468302 A/G, rs237902 C/T) was confirmed is this cohort; haplotype distribution revealed strong linkage disequilibrium (only 8/27 possible haplotypes, Fig). Morphine use, pain & nausea scores were significantly higher in women rs237902 CT or TT (19% of women) vs homozygotes for CC (Fig). There was no significant difference in morphine use between the 8 haplotypes (Fig). Persistent pain was present in 6% of women, and was not associated with any of the haplotypes or specific SNPs.
Our findings suggest that rs237902 genotype of OXTR influences morphine use, pain scores and nausea after cesarean delivery. We could not demonstrate an effect of any haplotype or single SNP on the incidence of chronic pain. Further well-designed studies are needed to elucidate the effects of OXTR variants at the receptor, expression or transcription levels, and examine in large prospective cohorts whether OXTR haplotypes are associated with protection from chronic pain.
1. Anesthesiology 2013;118:143-51
2. Int J Obstet Anesth 2010;19:254-60
3. ASA 2010, Abstract A590