Association between the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene and postoperative analgesic requirements

AbstractAn association between postoperative analgesic requirements in subjects who underwent orthognathic surgery and the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene was suggested by our previous genome-wide association study. To verify this association, we analyzed the association between the rs1465040 SNP and analgesic requirements, including opioid requirements, after open abdominal surgery. The association between the rs1465040 SNP and postoperative analgesic requirements was confirmed in the open abdominal surgery group (P = 0.036), suggesting that the TRPC3 SNP may contribute to predicting postoperative analgesic requirements

Genome-wide association study identifies polymorphisms associated with the analgesic effect of fentanyl in the preoperative cold pressor-induced pain test

Opioid analgesics are widely used for the treatment of moderate to severe pain. The analgesic effects of opioids are well known to vary among individuals. The present study focused on the genetic factors that are associated with interindividual differences in pain and opioid sensitivity. We conducted a multistage genome-wide association study in subjects who were scheduled to undergo mandibular sagittal split ramus osteotomy and were not medicated until they received fentanyl for the induction of anesthesia. We preoperatively conducted the cold pressor-induced pain test before and after fentanyl administration. The rs13093031 and rs12633508 single-nucleotide polymorphisms (SNPs) near the LOC728432 gene region and rs6961071 SNP in the tcag7.1213 gene region were significantly associated with the analgesic effect of fentanyl, based on differences in pain perception latency before and after fentanyl administration. The associations of these three SNPs that were identified in our exploratory study have not been previously reported. The two polymorphic loci (rs13093031 and rs12633508) were shown to be in strong linkage disequilibrium. Subjects with the G/G genotype of the rs13093031 and rs6961071 SNPs presented lower fentanyl-induced analgesia. Our findings provide a basis for investigating genetics-based analgesic sensitivity and personalized pain control. Keywords: Opioid sensitivity, Analgesia, Fentanyl, Polymorphism, GWA

Diversity of Opioid Requirements for Postoperative Pain Control Following Oral Surgery—Is It Affected by Polymorphism of the μ-Opioid Receptor?

We experience individual differences in pain and sensitivity to analgesics clinically. Genetic factors are known to influence individual difference. Polymorphisms in the human OPRM1 gene, which encodes the μ-opioid receptors, may be associated with the clinical effects of opioid analgesics. The purpose of this study was to determine whether any of the 5 common single-nucleotide polymorphisms (SNPs) of the OPRM1 gene could affect the antinociceptive effect of fentanyl. Fentanyl was less effective in subjects with the G allele of the OPRM1 A118G SNP than in those with the A allele, and subjects with the G allele required more fentanyl for adequate postoperative pain control than those with the A allele. In the future, identifying SNPs might give us information to modulate the analgesic dosage of opioid individually for better pain control. Factors underlying individual differences in sensitivity to pain other than genetic factors may include environmental and psychological factors. We therefore examined the effects of preoperative anxiety on the analgesic efficacy of fentanyl in patients undergoing sagittal split mandibular osteotomy (SSMO). From among the patients enrolled in the study, 60 patients (male/female: 18/42, age: 24.6 ± 6.7 years) who gave informed consent were examined for correlations between preoperative trait/state anxiety, as measured by the state-trait anxiety inventory (STAI) on the day before surgery, and postoperative consumption of patient-controlled analgesia (PCA) fentanyl and visual analog scale (VAS) assessment by patients. Levels of trait and state anxieties measured by the STAI were correlated with neither the consumption of PCA fentanyl nor postoperative VAS assessment. These findings suggest that psychological factors are unlikely to affect postoperative pain or the use of analgesics