| Background and ObjectivePain and preoperative anxiety are serious problem that we have to be faced with clinical anesthesia, and which will affect therapy smoothly of perioperative. Adequate release of pain and anxiety are necessary before and after operation to decrease the incidence of complication. As that to be considered, much things should be done with this.Since the completion of the Human Genome project in2003, there has been an increasing trend in medicine to correlate disease to genetic markers and phenotypic variance. The Human Genome Project revealed nearly complete genomic sequence data which provide the basis for further research on genomic variations influencing nociception, susceptibility to pain conditions, as well as response to pharmacotherapy. Polymorphisms of receptors, transporters, metabolizing enzymes, and other targets of pharmacotherapy and the nociceptive system are currently under investigation. Molecular mediators of pain processing such as inflammatory mediators (serotonin, histamine, bradykinin and cytokines), second messengers, receptors and endogenous neurotransmitters are under investigation, and will hopefully reveal new strategies for individualized pain management in the future.An individualized profile for patients at risk for severe pain or anxiety disorders, and a pharmacotherapy considering the patients’genetic background might considerably improve pain and anxiety disorders management. Research in the field of pain and anxiety management has revealed various genomic variations influencing sensitivity to pain, susceptibility to anxiety disorders. Future developments have to focus on the translation of these findings into clinical practice. Multiple genes are involved and single genes only have small contributions to the overall genetic impact. Up to now, however, most studies have addressed only one or a few single gene variations. The complexity of these genetic disorders still has to be elucidated.Our research aims the commonly candidate genetic polymorphism to determine the frequencies of COMTval158met and OPRM1A118G alleles in Chinese patients and to observe the associated impact of COMTval158met and OPRM1A118G on pain sensitivity and preoperative anxiety. The present study seem to provides an important foundation and theoretical evidence for the gene-directed treatment of pain and preoperative anxiety.Materials and MethodsSubjectsTwo hundred and eighty-four patients and twenty-eight healthy volunteers, aged20-50yr, within±20%of ideal body weight, and having an American Society of Anesthesiologists (ASA) physical status of I or II, undergoing selective operation were enrolled. Exclusion criteria included the following:known history of psychiatric disease, nervous disease, significant cardiovascular disease, hepatic or renal dysfunction, diabetes mellitus, alcohol or drug abuse, chronic analgesic use, pregnancy or nursing. All patients were of Chinese Han nationality and live in Henan province of China. The study design was approved by Institutional Ethics Committee of Zhengzhou University.Measurement of pain sensitivity and score of anxiety statePreoperatively, the pain threshold and pain tolerance threshold were measured three times using electrical stimulation and to recorded the average number. All patients to be enrolled in the trial accepted the investigation of anxiety state and recorded the score of SAI and TAI.Genotyping assays Venous blood samples (5ml) were collected from all patients in this study. DNA was extracted from leukocytes using a standard phenol/chloroform procedure. Genotyping of COMTval158met and OPRM1A118G alleles was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Statistical analysisSPSS12.0software was used for statistical analyses. Chi-square test was used to verify Hardy-Weinberg equilibrium. Data for the pain threshold, pain tolerance threshold, SAI and TAI score were compared among the genotype group using one-way analysis of variance with covariance analysis correction for multiple comparisons was performed before and after adjusted for age and weight. P-values <0.05were considered with statistically significant.Results General informationAmong the two hundred and eighty-four subjects, the mean of age was38.8years, and the mean of body mass index was18.4. Among the twenty-eight healthy volunteers, correspondingly, the mean of age was22.4years, and the mean of body mass index was15.6. There was no significant difference between patients and volunteers in general information except the age.Frequencies of OPRM1A118G and COMTval158metThe frequencies of COMTval158met and OPRM1A118G alleles in Chinese patients were0.342and0.321, respectively. The allele frequencies were in Hardy-Weinberg equilibrium.Effects of COMTval158met genetic polymorphism on pain sensitivity and preoperative anxietyThere was no significant differences in general information among the three genotype groups. PT and PTT were statistical different between met/met (1.6±0.9mA,4.5±1.1mA) and val/val (2.2±0.7mA,5.4±1.2mA) groups (P<0.05), SAI and TAI score were statistical different also between met/met (51.5±10.8,49.2±10.0) and val/val (44.4±9.5,43.1±7.3) groups (P<0.05), and there were no significant difference between val/val and val/met groups in PT, PTT, SAI and TAI score. However, compared with healthy volunteers’groups correspondingly, there were significantly lower in PT and PTT, and significantly higher in SAI score(P<0.05). There was no significant difference in TAI score(P>0.05).Association effects of COMTvall58met and OPRM1A118G genetic polymorphism on pain sensitivity and preoperative anxietyThere were twe hundreds and seventy-seven patients had carried out succeed in the joint genotyping. After association studied the COMTval158met and OPRM1A118G genetic polymorphism, they were divided into nine groups. Group A/A and val/val(n=68), group A/A and val/met(n=50), group A/A and met/met(n=17), group A/G and val/val(n=43), group A/G and val/met(n=46), group A/G and met/met(n=17), group G/G and val/val(n=18), group G/G and val/met(n=10), and group G/G and met/met(n=8). There was no significant differences in general information among the nine genotype groups. According to the neutral group A/G and val/met, there was significantly lower in PT at group G/G and val/met, and group G/G and met/met; there was significantly lower in PTT at group G/G and val/val, group G/G and val/met, and group G/G and met/met(P<0.05); there were significantly higher in SAI and TAI score at group A/G and met/met, and group G/G and met/met (P<0.05).Conclusions1. The COMTvall58met genetic polymorphism is a predisposing factor of preoperative anxiety. Compare with val158val and val158met, the patients with met158met genotype have the more probability in preoperative anxiety state.2. The COMTval158met genetic polymorphism would exacerbate the preoperative anxiety, and at the same time enhance pain sensitivity, through the remote effects on pain sensitivity.3. The OPRM1A118G genetic polymorphism is the main factor which affect pain sensitivity, the gene mutation of118G will enhance pain sensitivity and decrease the PT and PTT.4. There is no significantly relationship between the OPRM1A118G genetic polymorphism and preoperative anxiety. |
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