1. Human Opioid Receptor A118G Polymorphism Affects Intravenous Patient-controlled Analgesia Morphine Consumption after Total Abdominal Hysterectomy
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Bruno Jawan, Wen Ying Chou, Ping Hsin Liu, Chia Chih Tseng, Chien Cheng Liu, and C.-H. Wang
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Adult ,Genotype ,medicine.drug_class ,Analgesic ,Single-nucleotide polymorphism ,Pharmacology ,Hysterectomy ,Polymorphism, Single Nucleotide ,Opioid receptor ,medicine ,Humans ,Allele ,Infusions, Intravenous ,Receptor ,Alleles ,Pain Measurement ,Pain, Postoperative ,Polymorphism, Genetic ,Morphine ,business.industry ,Analgesia, Patient-Controlled ,Middle Aged ,Analgesics, Opioid ,Anesthesiology and Pain Medicine ,Opioid ,Postoperative Nausea and Vomiting ,Receptors, Opioid ,Female ,business ,medicine.drug ,Intravenous Patient-Controlled Analgesia - Abstract
Background: Animal and human studies indicate that genetics may contribute to the variability of morphine efficacy. A recent report suggested that cancer patients homozygous for the 118G allele caused by the single nucleotide polymorphism at nucleotide position 118 in the -opioid receptor gene require higher doses of morphine to relieve pain. The purpose of the current study was to investigate whether this polymorphism contributes to the variability of morphine efficacy in women who undergo abdominal total hysterectomy. Methods: After informed consent was obtained, 80 female patients (American Society of Anesthesiologist physical status I or II) scheduled to undergo elective total hysterectomy surgery were enrolled in this study. All patients received general anesthesia and were screened for A118G polymorphism by blood sample. Intravenous morphine patient-controlled analgesia was provided postoperatively for satisfactory analgesia. The authors recorded the morphine consumption doses and demand times. Pain at rest and side effects were measured with rating scales. Results: Forty-three women were A118 homozygous, 19 were heterozygous, and 18 were G118 homozygous. Patients homozygous for G118 required more morphine doses (33 10 mg) to achieve adequate pain relief compared with patients homozygous for A118 (27 10 mg) in the first 24 h (P 0.02). However, there was no statistically significant difference for morphine consumption at 48 h. Conclusion: Genetic variation of the -opioid receptor may contribute to interindividual differences in postoperative morphine consumption. In the future, identifying single nucleotide polymorphisms of patients may provide information to modulate the analgesic dosage of opioid for better pain control. IT has been known for a long time that the effects of morphine as an agent for pain control vary in different individuals. Morphine produces its clinical effects mainly through -opioid receptors. Polymorphisms in the -opioid receptor gene may be associated with the clinical effects of opioid analgesics, 1โ3 which encourages research into human genetic polymorphisms and their clinical consequences. Several single nucleotide polymorphisms (SNPs) have been identified in the human -opioid receptor gene. The A118G mutation is the most common one leading to a change in the gene product in the human -opioid receptors, which is an A to G substitution in exon 1 and results in an amino acid exchange at position 40 from asparagine to aspartate (N40D). 4 Functional effects of the A118G polymorphism have been demonstrated both in vitro and in vivo. In vitro, -endorphin has been shown to bind three times more tightly at the receptor of homozygous G allele than at that of homozygous A allele. 4 A recent report also suggested that cancer patients who were homozygous for the G118 variant required higher doses of oral morphine for long-term treatment of their pain. 2 Romberg et al. 5,6 studied the pharmacokinetics and pharmacodynamics of morphine-6-glucuronide (M6G), a -opioid agonist, and also found that A118G mutation of the human -opioid receptor gene reduced analgesic responses to M6G. The effect of -opioid receptor genotype on acute postoperative morphine requirements has not been reported; therefore, we decided to determine morphine consumption with intravenous patient-controlled analgesia in women undergoing total abdominal hysterectomy according to A118G polymorphism.
- Published
- 2006
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