Effect of μ-Opioid Receptor A118G Polymorphism on the ED50 of Epidural Sufentanil for Labor Analgesia

The promise of pharmacogenetics in labor analgesia…tantalizing, but not there yet

“…For example, there was significant overlap in the effective doses for the parturients with and without the A118G allele in both labor studies. 3,13 Indeed, in a third labor study in an urban North American population, the duration of intrathecal fentanyl 25 lg administered for labor analgesia was not different between parturients with and without the A118G allele. 9 In women who received intrathecal morphine 100 lg for post-cesarean analgesia, the mean 24-h intravenous morphine dose self-administered for breakthrough pain ranged from 5.9 mg in the homozygous A118 group to 9.4 mg in the homozygous 118G group.…”

“…1,2 Camorcia and colleagues have recently reported the results of the latest in a small series of studies examining the role of the A118G allele on the response to neuraxial opioid administered for labor analgesia. 3 Using an up-down sequential allocation method, the investigators provide evidence to support their hypothesis that the presence of the variant A118G allele results in a lower ED50 for epidurallyadministered sufentanil compared to parturients without the allele.…”

“…However, review of studies specific to laboring women, including the study by Camorcia et al adds confusion to this interpretation. 3 In a Swiss cohort of laboring women, Landau et al performed two intrathecal fentanyl dose-response studies, one using an up-down sequential allocation method (similar to the Camorcia et al study 3 ), and a second using a random-dose allocation method. 13 In both studies, the ED50 of intrathecal fentanyl was significantly lower (by a factor of 1.5-2.1) in parturients carrying at least one A118G allele.…”

“…22 Polymorphisms in ABCB1 have been shown to affect CNS opioid concentrations in some animal models, but not others, and with some opioids, but not others. In the two labor studies by Landau et al 13 and Camorcia et al 3 opioid was administered directly into the central nervous system; thus one wonders if mode of administration could play a role in the differential effect observed in some studies, but not others. Oertel et al 23 found brain region-specific changes in l-opioid receptor G-protein coupling efficacy in tissue from A118G individuals.…”

Analgesia for Childbirth: Modern Insights Into an Age-Old Challenge and the Quest for an Ideal Approach

“…Human genetic association studies have focused on polymor phisms of the OPRM1 gene, coding for µopioid receptors. The single nucleotide polymorphism OPRM 118A>G is associated with a decrease in pressure pain intensity and altered clinical response, but other candidate genes include those for COMT, fatty acid amide hydrolase and OPRD1 [99][100][101][102].…”