Pharmacogenetics has allowed clinicians to identify associations between an individual's genetic profile and his/her response to drugs. The A118G (c.188A>G)is a single nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1). The mutated protein, N40D, appears to increase the binding affinity and potency of beta-endorphin approximately 3-fold. Individuals carrying the variant receptor gene (A118G) may show differences in some of the functions mediated by beta-endorphin action at the altered OPRM1. Combined spinal-epidural (CSE) analgesia is a commonly utilized technique for labor analgesia. Analgesia is initiated with the intrathecal administration of a lipid-soluble opioid (e.g. fentanyl), sometimes combined with a local anesthetic. The mean (± SD) duration of analgesia after intrathecal fentanyl 25 microgram was 89 ± 43 min. The ED50 of intrathecal fentanyl for labor analgesia varies between 14 microgram to 18.2 microgram. The wide variability in the duration of analgesia, as was well the differences in ED50 may result from differences known to affect labor pain (e.g., ethnicity, parity, stage of labor). Another possible explanation for the differences in opioid requirements and duration, as well as incidence of side effects such as itching and nausea/vomiting, is that opioid responsiveness is determined by genetic variability of the µ-opioid receptor. The ED50 for intrathecal fentanyl labor analgesia was significantly lower for parturients carrying the A118G variant of the mu-opioid receptor, compared to parturients with the A118 wild type receptor. The purpose of this study is to determine whether polymorphism at nucleotide 118 of OPRM1 influences the duration of intrathecal opioid (fentanyl) labor analgesia, and intrathecal opioid (morphine) postoperative analgesia.
Name: Blood Draw
Description: Time from intrathecal drug administration to request for analgesia either in laboring women of after cesarean delivery
Measure: Duration of Intrathecal Fentanyl Analgesia Time: Time (0-1440 minutes) to first analgesia requestDescription: Time until request for supplemental analgesia following intrathecal morphine/fentanyl for cesarean delivery
Measure: Duration of Intrathecal Analgesia Following Cesarean Delivery Time: 0 to 72 hours following cesarean deliveryDescription: Visual analog pain scale (0 to 100) at 1st request for supplemental analgesia
Measure: Visual Analog Pain Scale (0 to 100) at Analgesia Request Following Intrathecal Intervention Time: VAS at analgesia requestDescription: Severity of pruritus during labor analgesia
Measure: Severity of Pruritus Following Fentanyl Time: Labor analgesiaDescription: Subjects reporting pruritus in the first 24 hours post cesarean delivery
Measure: Subjects With Pruritus at 24 Hours Post Morphine Time: 24 hours post cesarean deliveryCohort
There are 2 SNPs
The A118G (c.188A>G)is a single nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1). --- A118G ---
Individuals carrying the variant receptor gene (A118G) may show differences in some of the functions mediated by beta-endorphin action at the altered OPRM1. --- A118G ---
The ED50 for intrathecal fentanyl labor analgesia was significantly lower for parturients carrying the A118G variant of the mu-opioid receptor, compared to parturients with the A118 wild type receptor. --- A118G ---
SNP genotyping: For identification of allelic distribution of the A118G SNP, 20-60 ng of DNA from individuals will be first amplified by PCR (on thermocycler apparatuses equipped with a 96 well-microtiter plate block) using primers designed in the vicinity of the SNPs. --- A118G ---
The mutated protein, N40D, appears to increase the binding affinity and potency of beta-endorphin approximately 3-fold. --- N40D ---