Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. Although opioid sensitivity is well known to vary widely among individual subjects, several candidate genetic polymorphisms reported so far are not sufficient for fully understanding the wide range of interindividual differences in human opioid sensitivity. By conducting a multistage genome-wide association study (GWAS) in healthy subjects, we found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3–2q34 were strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery. The C allele of the best candidate single-nucleotide polymorphism (SNP), rs2952768, was associated with more analgesic requirements, and consistent results were obtained in patients who underwent abdominal surgery. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower ‘Reward Dependence' score on a personality questionnaire in healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated expression of a neighboring gene, CREB1. These results show that SNPs in this locus are the most potent genetic factors associated with human opioid sensitivity known to date, affecting both the efficacy of opioid analgesics and liability to severe substance dependence. Our findings provide valuable information for the personalized treatment of pain and drug dependence.

The purpose of this study was to investigate how grading according to our new gagging reflex index correlated with patient background and subsequent management. After obtaining institutional approval and informed consent, 110 patients with a gagging problem were enrolled. The patients completed the State-Trait Anxiety Inventory (STAI), the Dental Anxiety Scale (DAS), and a health questionnaire at initial consultation. On the second visit, an intra-oral examination was carried out and the severity of gag reflex determined according to our new, 5-level Classification of Gagging Problem (CGP) index: normal gagging but not desensitised (G1 = score 1); mild gagging (G2 = score 2); moderate gagging (G3 = score 3); severe gagging (G4 = score 4); and very severe gagging (G5 = score 5). No difference was found in grade based on age or STAI or DAS scores. The CGP score in male patients was significantly higher than that in female. The management classification method and degree of desensitisation were investigated retrospectively in each patient at 3 months and 1 year after initial consultation. The higher the CGP grade, the more often intravenous sedation or general anaesthesia was required due to difficultly in desensitisation. The present results suggest that determining whether it is possible to examine the molar area without inducing the gag reflex offers the key to deciding the treatment strategy.

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 m-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 OPRM1A118G SNP than in those with theA allele, and subjects with the G allele required more fentanyl for adequate postoperative pain control than those with theA 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 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 postoperativeVAS assessment. These findings suggest that psychological factors are unlikely to affect postoperative pain or the use of analgesics.

Management of patients with orofacial pain may benefit from a better understanding about patient factors that may lead pain chronicity. In this study, we retrospectively compared physical and psychological factors in patients with acute and chronic orofacial pain. We analyzed data from 854 patients presenting to the Orofacial Pain Center, Department of Dental Anesthesiology, Tokyo Dental College, Suidobashi Hospital between April 2010 and March 2014. We categorized patients into the acute group if their condition had persisted <6 months and the chronic group if their condition had lasted 6 months or longer, based on the classification by the International Association for the Study of Pain. The retrospective data were analyzed by using univariate analysis on background factors from a health questionnaire, pain evaluation sheet, and psychological test completed at the time of presentation. Multiple logistic regression was applied on these factors. Our results suggest that female gender and high trait anxiety may be involved in orofacial pain becoming chronic.

Background This study aimed to examine whether the combination of low-dose ketamine and propofol in deep sedation is clinically useful in controlling the behavior in intellectually disabled patients who are typically extremely noncooperative during dental procedures. Methods A total of 107 extremely noncooperative intellectually disabled adult patients were analyzed. In all patients, deep sedation was performed using either propofol alone (group P) or using a combination of propofol and 0.2 mg/kg or 0.4 mg/kg ketamine (groups PK0.2 and PK0.4, respectively). The procedures were performed in the order of insertion of nasal cannula into the nostril, attachment of mouth gag, and mouth cleaning and scaling. The frequency of patient movement during the procedures, mean arterial pressure, heart rate, peripheral oxygen saturation, recovery time, discharge time, and postoperative nausea and vomiting were examined. Results The three groups were significantly different only in the frequency of patient movement upon stimulation during single intravenous injection of propofol and scaling. Conclusion For propofol deep sedation, in contrast to intravenous injection of propofol alone, prior intravenous injection of low-dose ketamine (0.4 mg/kg) is clinically useful because it neither affects recovery, nor causes side effects and can suppress patient movement and vascular pain during procedures.