Effect of OPRM1 and COMT Gene Polymorphisms on the Analgesic Effect of Intrathecal Fentanyl During Labor Analgesia

Childbirth is considered one of the most painful events a woman may experience. Labor analgesia with an epidural or intrathecal opioids is an option that most women opt to receive nowadays. It has been hypothesized that genetic variability explains, at least in part, the large inter-individual variability in the observed response to neuraxial opioids. Pain perception and the analgesic response to opioids are most likely polygenic (affected by multiple single nucleotide polymorphisms across different candidate genes). The Landau Lab is investigating the association between the analgesic effect (potency) and duration of action of intrathecal fentanyl (ITF) in parturients and common polymorphisms of µ-opioid receptor gene (OPRM1) and catechol-O-methyltransferase (COMT) gene. We hypothesized that duration of ITF will be longer in A118 homozygotes of OPRM1 and Met158 of COMT (A/A-Met/Met) compared to women carrying a different allelic combination. We performed a secondary analysis on data from a study on 184 parturients receiving a combined-spinal epidural for labor analgesia. The primary outcome was duration of analgesia from ITF dose (25mcg) to request for additional analgesia (via epidural). There was no significant difference between genotypic groups (p=0.358) although there was a trend for longer duration of ITF in A/A-Met/Met women [n=38; 81min (CI 95% 70, 92)] compared to Met/Met not A/A women [n=11; 63min (CI 95% 46, 80]. These findings suggest that genetic variants of OPRM1 and COMT genes may affect the response to intrathecal fentanyl for labor analgesia and warrant further investigation as this may have relevant clinical implications.