The Influence Of Gene Polymorphism And Pain Sensitivity On Sufentanil Analgesic Effect For Postoperative Pain

Background:Postoperative acute pain is a common complaint in postoperative patients,but the situation of present analgesic therapies is not satisfying.The analgesic efficacy of opioids exhibits significant individual differences.The diversity of pain sensitivity and genetic polymorphism are important influencing factors.Also,genetic factors may influence one's perception to pain and change the expression of metabolic enzymes and/or receptors,resulting the difference of clinical analgesic effect.A member of the opioids,Sufentanil,which with strong analgesic efficacy and less adverse reactions,is widespread used in postoperative pain management.This study was performed to observe the influence of pain sensitivity and some common mutations in the Han population,like OPRM1 A118G?CYP3A4*1G?COMT Val158Met and ABCB1 3435C>T,on sufentanil analgesic effect in laparoscopic total hysterectomy Han patients.This present study provides an significant theoretical evidence for the gene-directed,rationalized and personalized medication in the pain treatment with sufentanil.Materials and methodsSubjectsPatients undergoing selective laparoscopic total hysterectomy with general anesthesia and accepted intravenous analgesia treatment were chosen,aged 18-65 years,being at American Society of Anesthesiologists(ASA)physical status of I or?.Exclusion criteria included the following conditions:long-term smoking,known history of alcohol or drug abuse,chronic pain,psychiatric illness and poor control of medical disease.The study design was endorsed by the Medical Ethics Committee of Zhujiang Hospital and all of the subjects signed informed consent.Anesthesia and AnalgesiaThe pain threshold and pain tolerance threshold were measured using Electronic Von Frey Stimulator the day before surgery.A standardized endotracheal general anesthesia technique was used for all patients.When a patient complained of obvious pain discomfort or restlessness after the surgery,5?g sufentanil was given as the analgesic first agent,then the patient-controlled intravenous analgesia was started.The degree of pain during PCIA treatment was assessed with numerical rating scale(NRS).Follow-up assessments were made at 1,2,4,6,24 and 48 hours after the surgery,and the NRS scores,sufentanil consumption and occurrence of any adverse effects were recorded at each time point.The total capacity of the PCIA pump was 100ml,contained sufentanil 2.0?g·kg-1,Tropisetron mesylate 12mg and normal saline.The PCIA pump was set to give a 1ml bonus of sufentanil solution with 15 min lockout time,2ml/h background infusion.Gene extraction and detectionThe DNA extraction kit of BioTeKe Corpration Company was used to extract DNA.The Sequenom MassArray System was used to make genotyping.Statistical AnalysisAll statistical analyses were carried out by the statistical software IBM SPSS Statistics for windows version 20.0.Descriptive data were expressed as mean ?standard deviations(mean ? SD).The relationships between the variables used linear correlation analysis.One-way analysis of variance was used to assess whether the measurement data was different among groups.Covariance analysis was used to compare the pain threshold,pain threshold and sufentanil consumption in different genotype groups.P-value<0.05 was considered statistically significant.ResultsPart 1:The correlation between preoperative pain sensitivity and perioperative opioids doses in surgical patients118 subjects were included,the mean preoperative pain threshold was 89.37±37.79Gr,pain tolerance threshold was 126.30Gr.The occurrence rate of postoperative nausea and vomiting(PONV)within 48h in the study was 29.7%.20.3%patients were in a state of mild sedation within 24h after surgery.Other side effects such as pruritus and respiratory depression were not occurred.Both of preoperative pain threshold and pain tolerance threshold were correlated with unit time dosage of remifentanil during the anesthesia.Pain threshold showed correlation with sufentanil consumption at the early time(within 6h)after the operation,and also correlated with the first hour' NRS score.Pain tolerance threshold showed no obvious correlation with NRS scores or sufentanil consumption.part 2:The impact of gene polymorphism on pre-operative pain sensitivity and sufentanil analgesic effect in surgical patients97 patients were included.The mutant allele frequency was 31.96%for OPRM1 A118G,26.8%for CYP3A4*1G,23.71%for COMT Val158Met and 36.08%for ABCB1 3435C>T.The postoperative pain was generated earlier in COMT Val158Met wild group than mutant group.Also,patients in COMT Val158Met wild-type genotype consumed much sufentanil.Patients in OPRM1 A118G mutant genotype group had higher NRS scores than wild group within 4h after surgery.There were no significant differences among different genotypes of CYP3A4*1G and ABCB1 3435C>T.The occurrences of postoperative side effects were comparable.Combining OPRM1 A118G and COMT Val158Met,we found that patients with mutant-type of OPRM1 A118G and wild-type of COMT Val158Met felt postoperative pain earlier than other groups,and also consumed much sufentanil than other groups.Conclusions1.Patients,those who are with the higher preoperative pain sensitivity,consume more remifentanil during surgery.2.The sufentanil consumption of early time after surgery is demanded more in patients who have the lower of the preoperative mechanical pain threshold.3.At the early time after surgery,the mutants of OPRM1 A118G have a higher degree of pain than the wild-type.4.Compared to the wild-type homozygotes of COMT Val158Met,the mutants consume less sufentanil in postoperative analgesia.