The role of hydromorphone and OPRM1 in postoperative pain relief with hydrocodone

• Published in: Pain physician 2013-05, Vol.16 (3), p.E227-E235
• Main Authors: Boswell, Mark V, Stauble, M Elaine, Loyd, Gary E, Langman, Loralie, Ramey-Hartung, Bronwyn, Baumgartner, Richard N, Tucker, William W, Jortani, Saeed A
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Analgesics, Opioid - blood; Analgesics, Opioid - therapeutic use; Cesarean section; Chromatography, Liquid; Female; Genotype; Humans; Hydrocodone - blood; Hydrocodone - therapeutic use; Hydromorphone - blood; Hydromorphone - metabolism; Middle Aged; Morphine; Narcotics; Obstetric Surgical Procedures - adverse effects; Pain; Pain, Postoperative - blood; Pain, Postoperative - drug therapy; Pain, Postoperative - genetics; Patients; Pharmacogenetics; Polymorphism, Single Nucleotide - genetics; Postoperative period; Receptors, Opioid, mu - genetics; Signal transduction; Tandem Mass Spectrometry; Young Adult
• ISSN: 1533-3159; 2150-1149
• DOI: 10.36076/ppj.2013/16/E227

Postoperative pain management remains a challenge for clinicians due to unpredictable patient responses to opioid therapy. Some of this variability may result from single nucleotide polymorphisms (SNPs) of the human opioid mu-1 receptor (OPRM1) that modify receptor binding or signal transduction. The OPRM1 variant with the highest frequency is the A118G SNP. However, previous studies have produced inconsistent results regarding the clinical effects of A118G on opioid response. We hypothesized that measurement of serum opioid concentrations, in addition to determining total opioid consumption, may provide a more precise method of assessing the effects of A118G on analgesic response. The current study evaluated the relationship of analgesia, side effects, total hydrocodone consumption, quantitative serum hydrocodone and hydromorphone concentrations, and A118G SNP in postoperative patients following Cesarean section. 158 women scheduled for Cesarean section were enrolled prospectively in the study. The patients had bupivacaine spinal anesthesia for surgery and received intrathcal morphine with the spinal anesthetic or parenteral morphine for the first 24 hours after surgery. Thereafter, patients received hydrocodone/acetaminophen for postoperative pain control. On postoperative day 3, venous blood samples were obtained for OPRM1 A118G genotyping and serum opioid concentrations. 131 (82.9%) of the subjects were homozygous for the 118A allele of OPRM1 (AA) and 27 (17.1%) carried the G allele (AG/GG). By regression analysis, pain relief was significantly associated with total hydrocodone dose in the AA group (P = 0.01), but not in the AG/GG group (P = 0.554). In contrast, there was no association between pain relief and serum hydrocodone concentration in either group. However, pain relief was significantly associated with serum hydromorphone concentration (a metabolite of hydrocodone) in the AA group (P = 0.004), but not in the AG/GG group (P = 0.724). Conversely, side effects were significantly higher (P < 0.04) in the AG/GG group (mean = 6.4) than in the AA group (mean = 4.4), regardless of adjustment for BMI, pain level, or total dose of hydrocodone. This study found a correlation between pain relief and total hydrocodone dose in patients homozygous for the 118A allele (AA) of the OPRM1 gene, but not in patients with the 118G allele (AG/GG). However, pain relief in 118A patients did not correlate with serum hydrocodone concentrations, but rather with serum hy