A variant in the SCN10A enhancer may affect human mechanical pain sensitivity.

Expression of Nav1.8, encoded by SCN10A, can affect pain transmission and thus mediate the human pain phenotype. In the current study, we assessed whether the variant rs6801957, located in the SCN10A enhancer region, may have the potential to affect human pain. Through dual-luciferase reporter assays in 293T cells, we found that the SCN10A enhancer A (Enh-A) increased the activity of the SCN10A promoter ( P < 0.05). Additionally, in a cohort of 309 healthy women, mutant rs6801957 A/A was found to have a significant association with decreased human experimental mechanical pain sensitivity ( P < 0.05). We then found that mutant genotype A/A suppressed the increased effect of Enh-A compared with wild-type G/G ( P < 0.05). The association between rs6801957 and human experimental mechanical pain sensitivity was further validated in a larger cohort of 1005 women ( P < 0.05). In conclusion, these results demonstrated that the variant rs6801957 and Enh-A may affect SCN10A gene expression and play an important role in human mechanical pain sensitivity.

A SCN10A SNP biases human pain sensitivity.

BACKGROUND: Nav1.8 sodium channels, encoded by SCN10A, are preferentially expressed in nociceptive neurons and play an important role in human pain. Although rare gain-of-function variants in SCN10A have been identified in individuals with painful peripheral neuropathies, whether more common variants in SCN10A can have an effect at the channel level and at the dorsal root ganglion, neuronal level leading to a pain disorder or an altered normal pain threshold has not been determined. RESULTS: Candidate single nucleotide polymorphism association approach together with experimental pain testing in human subjects was used to explore possible common SCN10A missense variants that might affect human pain sensitivity. We demonstrated an association between rs6795970 (G > A; p.Ala1073Val) and higher thresholds for mechanical pain in a discovery cohort (496 subjects) and confirmed it in a larger replication cohort (1005 female subjects). Functional assessments showed that although the minor allele shifts channel activation by -4.3 mV, a proexcitatory attribute, it accelerates inactivation, an antiexcitatory attribute, with the net effect being reduced repetitive firing of dorsal root ganglion neurons, consistent with lower mechanical pain sensitivity. CONCLUSIONS: At the association and mechanistic levels, the SCN10A single nucleotide polymorphism rs6795970 biases human pain sensitivity.

BiOxCly/BiOmBrn/BiOpIq/GO quaternary composites: Syntheses and application of visible-light-driven photocatalytic activities.

Herein, the preparation of numerous bismuth oxychloride/bismuth oxybromide/bismuth oxyiodide/graphene oxide (BiOxCly/BiOmBrn/BiOpIq/GO) composites is reported. A facile hydrothermal method was employed to synthesize these photocatalysts, which had various GO contents. A total of 10 bismuth-oxyhalide composites were isolated and characterized using FE-SEM, XRD, FE-TEM, UV-Vis-DRS, FT-IR, EPR, HR-XPS, PL, and BET. The photocatalytic efficiencies of these 10 bismuth-oxyhalide composites were measured under visible-light irradiation by estimating the concentration of 2-hydroxybenzoic acid (HBA) degradation. The findings indicated that the rate constant order of the HBA degradations was BiOCl/BiOBr/BiOI/GO > Bi3O4Cl/Bi3O4Br/Bi4O5I2/GO > Bi12O17Cl2/Bi3O4Cl/Bi12O17Br2/ Bi7O9I3/GO > Bi12O17Cl2/BiOBr/BiOI/GO > Bi12O17Cl2/Bi12O17Br2/Bi7O9I3/Bi5O7I/GO > Bi3O4Cl/BiOBr/Bi3O4Br/Bi4O5I2 > Bi3O4Cl/BiOBr/BiOI > BiOCl/BiOBr/BiOI > Bi12O17Cl2/Bi5O7Br/Bi5O7I > GO. A maximum rate constant of 0.191 h-1 was reached for BiOCl/BiOBr/BiOI/GO, providing photocatalytic efficiency that was eight times higher than that of composite BiOCl/BiOBr/BiOI. We also proposed a photocatalytic mechanism demonstrating that O2-, h±, OH, and 1O2 are all essential for HBA degradation.

Bismuth oxyfluoride/bismuth oxyiodide nanocomposites enhance visible-light-driven photocatalytic activity.

This is the first paper to report a series of bismuth oxyfluoride/bismuth oxyiodide (BiOpFq/BiOxIy) nanocomposites with different F/I molar ratios, pH values, and reaction temperatures that were synthesized through a template-free and controlled hydrothermal method. These nanocomposites were characterized through scanning electron microscope energy dispersive microscopy (SEM-EDS), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET), and diffuse reflectance spectroscopy (DRS). Under visible-light irradiation, the BiOpFq/BiOxIy composites exhibited excellent photocatalytic activities in the degradation of crystal violet (CV) and 2-hydroxybenzoic acid (HBA). The order of rate constants was BiOF/BiOI > BiOI ≫ BiOF. The photocatalytic activity of BiOF/BiOI composites reached a maximum rate constant of 0.2305 h-1, 1.2 times higher than that of BiOI and 100 times higher than that of BiOF. Thus, the derived BiOF/BiOI is crucial for photocatalytic activity enhancement. After the removal of CV in the third cycle, no apparent deficits in photocatalytic activity were observed, and the observed deficit was 8.2% during the fifth run. Overall, the catalytic activity and stability observed for the proposed composites were determined to be adequate under visible-light irradiation. For various scavengers, the noted quenching effects demonstrated that reactive O2- has a notable role in the degradation of the applied CV.

Effects of Epidemiological Factors and Pressure Pain Measurements in Predicting Postoperative Pain: A Prospective Survey of 1,002 Chinese Patients.

BACKGROUND: A high degree of inter-individual differences was noted in human basal pain as well as the reporting of clinical pain, such as postoperative pain. Understanding the effects of common epidemiological variations and preoperative experimental methods of human pain perception may contribute to individualized pain treatment for patients. OBJECTIVES: The current study was aimed to assess the role of epidemiological factors and preoperative experimental pain sensitivity for predicting postoperative pain and to analyze the potential effects of epidemiological factors on experimental pain sensitivity. STUDY DESIGN: A prospective survey of patients who were scheduled for selective surgery under general anesthesia. SETTING: Department of Anesthesiology at a teaching hospital in a medical college in a major metropolitan city in China. METHODS: One thousand two Chinese patients who were scheduled for selective surgery under general anesthesia were included. The preoperative epidemiology data of all patients were collected by the investigator through face-to-face interviews, and pressure pain, including the pressure pain threshold and tolerance, was tested. Next, the pain intensity and consumption of patient-controlled analgesia during the 48 hours after surgery were followed up. RESULTS: Through regression analysis of the current prospective study, epidemiological factors, including current smoker (P = 0.002), history of surgery (P = 0.038), and lower preoperative pressure pain tolerance (P = 0.001), were identified as independent risk factors for the incidence of postoperative inadequate analgesia. Additionally, from the perspective of the postoperative analgesia outcome, minimally invasive surgery and procedure-specific pain-treatment should be encouraged. Furthermore, several factors, including gender and smoking status, were found to be associated with the postoperative analgesic requirement or basal pressure pain threshold. LIMITATIONS: The limitations of this study include that preoperative psychological tests were not performed. CONCLUSIONS: Preoperatively determining the smoking status and history of surgery might serve as predictors for postoperative analgesia in the Chinese population. Additional preoperative pressure pain measurements might be an effective experimental method for predicting postoperative pain.Key words: Epidemiologic, pressure pain, smoking, predicting, surgery, postoperative pain, inadequate analgesia, Chinese population.

Phenotypes and Genotypes in Five Children with Congenital Insensitivity to Pain with Anhidrosis.

BACKGROUND: Congenital insensitivity to pain with anhidrosis is an extremely rare hereditary disorder linked to variants in NTRK1. Our goal was to characterize the clinical features and the genetic basis of the disorder in Chinese patients. METHODS: Patients were enrolled via social networking. Clinical features were investigated by interview, chart review, and physical examination. DNA was extracted from peripheral blood to genotype NTRK1 in patients and their parents. Variants identified were checked against a control cohort by high-throughput sequencing, and the effects of these variants were assessed in silico. RESULTS: Clinical features in five patients were cataloged, and six loss-of-function NTRK1 variants were identified, including a frameshift variant c.963delG, a nonsense variant c.1804C>T, an intron variant c.851-33T>A, and three missense variants c.1802T>G, c.2074C>T, and c.2311C>T. CONCLUSIONS: The results expand the spectrum of clinical and genetic features of congenital insensitivity to pain with anhidrosis and will help facilitate analysis of genotype-phenotype association in the future.

To predict sufentanil requirement for postoperative pain control using a real-time method: A prospective observational cohort study.

Preoperative identification of individual sensitivity to opioid analgesics could improve the quality of postoperative analgesia. We explored the feasibility and utility of a real-time assessment of sufentanil sensitivity in predicting postoperative analgesic requirement.Our primary study included 111 patients who underwent measurements of pressure and quantitative pricking pain thresholds before and 5 minutes after sufentanil infusion. Pain intensity was assessed during the first 24-hour postsurgery, and patients who reported inadequate levels of analgesia were excluded from the study. The sufentanil requirement for patient-controlled analgesia was recorded, and a subsequent exploratory study of 20 patients facilitated the interpretation of the primary study results. In the primary study, experimental pain thresholds increased (P < 0.001) 5 minutes after sufentanil infusion, and the percent change in pricking pain threshold was positively associated with sufentanil requirement at 12 and 24 hours after surgery (ß = 0.318, P = 0.001; and ß = 0.335, P = 0.001). A receiver-operating characteristic curve analysis showed that patients with a change in pricking pain threshold >188% were >50% likely to require more sufentanil for postoperative pain control. In the exploratory study, experimental pain thresholds significantly decreased after the operation (P < 0.001), and we observed a positive correlation (P < 0.001) between the percent change in pricking pain threshold before and after surgery. Preoperative detection of individual sensitivity to sufentanil via the above described real-time method was effective in predicting postoperative sufentanil requirement. Thus, percent change in pricking pain threshold might be a feasible predictive marker of postoperative analgesia requirement.

Genotypic Analysis of SCN9A for Prediction of Postoperative Pain in Female Patients Undergoing Gynecological Laparoscopic Surgery.

BACKGROUND: The SCN9A gene product is a critical component in human pain perception. Recent studies found that single-nucleotide polymorphisms (SNPs) in this gene contributed to the risk and severity of common pain phenotypes. OBJECTIVES: In this study, we aimed to assess the use of SCN9A SNP screening for predicting postoperative pain. STUDY DESIGN: A retrospective assessment of patients who underwent gynecological laparoscopic surgery. SETTING: Department of anesthesiology, a teaching hospital, in a medical college, major metropolitan city, China. METHODS: Twenty-nine candidate and tag SCN9A SNPs were analyzed in this study. Four hundred twenty-one patients who underwent gynecological laparoscopic surgery and refused postoperative patient controlled analgesia (PCA) were recruited and completed the study protocol. An additional 578 patients who voluntarily received PCA treatment were included for verification. Postoperative pain intensity was evaluated in all patients using numerical rating scale (NRS), and for patients receiving PCA analgesic requirements were also recorded. OUTCOMES ASSESSMENT: The outcome was assessment of postoperative pain NRS and PCA analgesic requirements. RESULTS: Ten different SCN9A SNPs exhibited significant associations with postoperative pain intensity, the incidence of severe postoperative pain, and postoperative PCA requirement. Of the candidate SCN9A SNPs, there was a statistically significant correlation between SNP rs6746030 and higher maximum NRS scores during the postoperative follow-up of non-PCA patients (P < 0.05). Furthermore, there was a significant association between the tag SNP rs4286289 and both increased postoperative maximum NRS scores (P < 0.05) and higher incidences of severe postoperative pain (P < 0.05) in non-PCA patients. Meanwhile, in PCA patients, rs4286289 exhibited the strongest association (P = 0.001) with increased requirements for postoperative analgesics, which indirectly strengthened the significant association between this SNP and higher postoperative pain. LIMITATIONS: The limitations of this study include that it is an assessment of only Chinese women scheduled for gynecological laparoscopic surgery. CONCLUSION: The current study provides evidence that postoperative pain was affected by SCN9A variability in gynecological patients. Notably, our results provide the first indication that SCN9A SNP rs4286289 can be used as a predictor for hypersensitivity to postoperative pain.

The Effect of SCN9A Variation on Basal Pain Sensitivity in the General Population: An Experimental Study in Young Women.

UNLABELLED: SCN9A is a key player in various rare monogenic pain disorders, including absence of pain or extreme pain, indicating that SCN9A is critical in human pain perception. This study aimed to investigate the association between the single-nucleotide polymorphisms (SNPs) in SCN9A and basal pain sensitivity variability in the general population. We used a combined tag and candidate SNP approach to explore possible associations between SCN9A SNPs and basal pain sensitivity in 309 healthy female Chinese undergraduates. Mechanical and heat pain sensitivity were measured, and a total of 28 SNPs were included in the final correlation analysis. Four candidate SNPs (rs6746030, rs7595255, rs12622743, and rs11898284) and 10 tag SNPs were associated (P < .05) with different pain perception phenotypes and exhibited opposite effects, resulting in either hypersensitivity or hyposensitivity. Furthermore, of all these SNPs, rs16851778 showed the strongest significant (P = .003) association with lower mechanical pain sensitivity, which was strengthened in a subsequent replication sample with 260 young patients scheduled for elective gynecological surgery. These findings provided evidence that the variability of basal pain sensitivity was associated with SCN9A polymorphisms in the general population. PERSPECTIVE: This study demonstrated that several candidate and tag SCN9A SNPs were associated with hypersensitivity or hyposensitivity to basal experimental pain stimulation. Moreover, we identified a novel SNP, i,e,, rs16851778, that was associated with lower mechanical pain sensitivity and that was strengthened in a subsequent replication sample.