Genetic And Nongenetic Factors Associated With Pain Sensitivity And Postoperative Fentanyl Dose

Objective:To investigate the respective influence of patient characteristics,μ-opioid receptor A118G polymorphism,cytochrome P450 3A4^* 18A polymorphism,catechol-O-methyltransferase Val158Met polymorphism and psychological variables on electrical and chemical pain,ischemic pain sensitivity and to explore the impact of these genetic and nongenetic factors on cumulative 24-hour and 48-hour dose requirements of fentanyl after abdominal surgery.Methods:Ninety-nine patients(American Society of Anesthesiologist physical statusâ… -â…¢)scheduled to undergo elective abdominal surgery were included in this study.They were assessed for anxiety,depression and personality on the night before surgery.All patients received general anesthesia and abdominal surgery half an hour after they were measured the responses to electrical and chemical, ischemic pain.They were screened for OPRM1 AllSG polymorphism, CYP3A4^* 18A polymorphism and COMT Val158Met polymorphism by blood samples.Intravenous fentanyl patient-controlled analgesia was provided postoperatively for satisfactory analgesia.The cumulative 24-hour and 48-hour postoperative dose of fentanyl and postoperative side effects were recorded.We analyzed all collected data using multiple stepwise regression analysis to investigate whether these variables contributed to the variability of experimental pain sensitivity and postoperative fentanyl dose.Results:â‘ There were forty-nine homozygous 158Val/Val(50.5%), thirty-six heterozygous 158Val/Met(37.1%),and twelve homozygous 158Met/Met(12.4%)in ninety-seven patients,the frequency COMT Val158Met variant allele in our patients was 0.309;there were ninety homozygous ^*1/^*1(92.8%),seven heterozygous ^*1/^*18A(7.2%)in ninety-seven patients,the frequency CYP3A4^* 18A variant allele in our patients was 0.036;there were thirty-one homozygous 118AA(41.9%), thirty-one heterozygous 11 SAG(41.9%),and twelve homozygous 118GG (16.2%)in seventy-four patients,the frequency OPRM1 A118G variant allele in our patients was 0.372;â‘¡For electrical and chemical stimulation,pain threshold ranged from 0.20 to 3.17mA,pain tolerance ranged from 1.13 to 5.60mA;for ischemic stimulation,pain threshold ranged from 15 to 1080 second,pain tolerance ranged from 100 to 2050 second;â‘¢The main factors affecting electrical and chemical pain threshold included OPRM1 A118G genotype,the preoperative trait anxiety,weight and occupation;patients with homozygous 118GG had significantly higher pain threshold compared to those homozygous 118AA(P=0.017);the main factors affecting pain tolerance included age,weight,smoking and the preoperative trait anxiety,patients under 50 years old had significantly higher pain tolerance compared to those over or equal to the age of 50 years(P=0.033);â‘£The main factors affecting ischemic pain threshold included COMT Val158Met genotype, drinking and OPRM1 A118G genotype;⑤The cumulative 24-hour postoperative dose of fentanyl ranged from 0.004 to 0.038 mg/kg, 48-hour postoperative dose ranged from 0.011 to 0.053 mg/kg;â‘¥The main factors affecting 24-hour and 48-hour postoperative dose of fentanyl included the preoperative state anxiety,COMT Val158Met genotype, weight and age;patients who experienced higher levels of preoperative state anxiety needed higher fentanyl dose compared with those who experienced lower levels of preoperative state anxiety(P₂₄=0.000, P₄₈=0.001);⑦Preoperative electrical and chemical,ischemic pain threshold and tolerance showed no association with postoperative dose of fentanyl(P＞0.05);⑧During the first 48 hours after surgery the incidence of nausea and vomiting was 31.3%and 27.3%,the incidence of dizziness and drowsiness was 59.6%and 33.3%respectively,all of them showed no association with postoperative dose of fentanyl(P＞0.05),none of the study patients had respiratory depression.Conclusions:â‘ For electrical and chemical stimulation the most important factor affecting pain threshold was OPRM1 A118G genotype, and the most important factor affecting pain tolerance was age;â‘¡For ischemic stimulation the most important factor affecting pain threshold was COMT Val158Met genotype;â‘¢The major factors affecting postoperative dose of fentanyl were the preoperative state anxiety,COMT Val158Met genotype,weight and age;and the most important factor was the preoperative state anxiety;â‘£The preoperative pain threshold could not predict postoperative dose of fentanyl.