Heterogeneity of clinical features and mutation analysis of NTRK1 in Han Chinese patients with congenital insensitivity to pain with anhidrosis.

PURPOSE: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited disorder whose core clinical features consist of no response to noxious stimuli and inability to sweat under any conditions. Our goal was to characterize the details of phenotypic and genotypic features in Chinese CIPA patients. PATIENTS AND METHODS: Personal data and clinical information were investigated by interview and physical examination. DNA was extracted from blood samples of patients and their available familial members and subjected to genetic analysis. RESULTS: A total of 41 Han Chinese CIPA patients from 35 unrelated families were recruited. The distribution of patients was mainly in the central and southern regions of China, with a male to female ratio of 3:1 and a mortality rate of 7.3%. Heterogeneity of clinical features, including pain insensitivity, temperature sensation, and complications, were cataloged. Interestingly, some patients had "visceral pain" sensation, and there was a significant difference in temperature perception and thermal pain between individuals. The incidence of bone and joint fractures was 49%. The characteristics of 19 mutations of NTRK1 in 41 patients, with five novel mutations, were identified. More than 63% of patients had the splice mutation, c.851-33 T>A, which strongly suggests that it may be a common pathogenic site in Han Chinese patients. CONCLUSION: Current findings expand our knowledge about the spectrum of phenotypic features and the racial characteristics of NTRK1 mutations of CIPA patients in the Han Chinese population.

Phenotypic and genotypic features of a pair of Chinese identical twins with congenital insensitivity to pain and anhidrosis: A case report.

RATIONALE: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disorder characterized by insensitivity to noxious stimulus and the absence of sweating. Fractures and joint destruction are common complications, but detailed studies on mineral and skeletal homeostasis are not available. Mental retardation is often reported, but detailed observations during childhood are lacking. PATIENT CONCERNS: A pair of 46-month-old Chinese identical twin brothers was presented at our hospital. The brothers had the typical manifestations of insensitivity to noxious stimulus, inability to sweat, and recurrent episodes of unexplained fever. Fortunately, they did not present common complications such as self-mutilation, trauma, bruise, and repeated bone fractures. DIAGNOSES: Two novel compound heterozygous variants of NTRK1 (c.632T > A and c.1253_1254delTC) were identified. INTERVENTIONS: The patients were subjected to routine and specialist clinical examinations. Daily care and symptomatic treatment were given. OUTCOME: X-ray films of proband 2 showed a fracture in the first metatarsal. Decreased bone mineral density (BMD) and mild-to-moderate retardation of the Gesell developmental schedules (GDS), especially language and adaptability, were observed. Evaluation results for BMD and GDS in proband 2 were worse than those in his brother. LESSONS: The current findings expand our knowledge about the spectrum of phenotypic and genotypic features of CIPA, which will help facilitate future genotype-phenotype association studies. Daily care by parents promotes favorable outcomes in patients.

Increased Nav1.7 expression in the dorsal root ganglion contributes to pain hypersensitivity after plantar incision in rats.

Postoperative pain remains a complex problem that is difficult to manage in the clinical context, seriously affecting rehabilitation and the quality of life of patients after surgery. Nociceptors, of which the cell bodies are located in the dorsal root ganglion, are crucial for initiating and conducting the pain signal. The peripheral voltage-gated sodium channels, including Nav1.7, which is mainly expressed in the dorsal root ganglion, are key to understanding the mechanism underlying postoperative pain. Nav1.7, in particular, of which mutations in the encoding gene ( SCN9A) can determine whether pain occurs, has aroused most attention. Previous studies have shown that Nav1.7 in dorsal root ganglion is critical for the development of inflammatory pain and some neuropathic pain. However, the expression of Nav1.7 in the dorsal root ganglion after surgery and its role in postoperative pain hypersensitivity remain unclear. Therefore, in this study, in order to gain a better understanding of the role of dorsal root ganglion Nav1.7 in pain hypersensitivity following operation, we dynamically examined the pain-related behavior and expression of Nav1.7 in L4-L6 dorsal root ganglion before and after plantar incision in rats (an acute postoperative pain model). After plantar incision, the mechanical and thermal pain threshold decreased significantly, the cumulative pain score was increased significantly, meanwhile quantitative polymerase chain reaction and Western blotting results showed that expression of Nav1.7 in L4-L6 dorsal root ganglion was enhanced significantly. After pretreatment using SCN9A-RNAi-LV delivered via an intrathecal tube, immunohistochemistry showed that increased expression of Nav1.7 in L4-L6 dorsal root ganglion after plantar incision was inhibited, as also confirmed by quantitative polymerase chain reaction and Western blotting. Moreover, pain hypersensitivity was alleviated. These results suggested that Nav1.7 of L4-L6 dorsal root ganglion plays an important role in the development of pain hypersensitivity after plantar incision.

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.

Associations between single-nucleotide polymorphisms in the NTRK1 gene and basal pain sensitivity in young Han Chinese women.

OBJECTIVES: The NTRK1 gene plays an important role in sensory and sympathetic neuronal survival. Mutations in this gene cause a rare hereditary disease known as congenital insensitivity to pain with anhidrosis. The aim of this study was to explore possible associations between single-nucleotide polymorphisms (SNPs) in NTRK1 and pain perception in a selected population. METHODS: A total of 309 healthy Han Chinese female undergraduates were recruited. Responses to quantitative sensory testing of pressure pain (dull, sharp, and acupuncture) were assessed, and genotyping of 13 tag-SNPs of NTRK1 was performed in the undergraduates recruited. Association analyses were performed via logistic regression analysis after adjusting for covariates such as age and body mass index. Promising associations were replicated in 197 patients scheduled to undergo gynecological surgery. RESULTS: The results showed that nine tag-SNPs of NTRK1 were significantly associated with pressure pain thresholds (P<0.05), leading to either hypersensitivity or hyposensitivity. More specifically, four tag-SNPs, rs1800880, rs6334, rs2644604 and rs943552, revealed a highly significant (P=0.008, 0.02, 0.01, 0.01, respectively) association with lower mechanical pain sensitivity of sharp pressure pain. Individuals who carried the haplotype CTCC were hyposensitive to sharp pressure pain compared with other haplotypes. CONCLUSION: These results suggest that polymorphisms in NTRK1 play an important role in pain sensitivity in young Han Chinese women.

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.

SCN11A variants may influence postoperative pain sensitivity after gynecological surgery in Chinese Han female patients.

Nav1.9, encoded by sodium voltage-gated channel alpha subunit 11 (SCN11A), is one of the main sodium channels involved in pain transmission. Dysfunction of Nav1.9 alters pain sensitivity, resulting in insensitivity to pain or familial episodic pain. Our purpose was to explore the effects of SCN11A single-nucleotide polymorphisms (SNPs) on postoperative pain sensitivity in Chinese Han female patients after gynecological surgery.Here, we combined the methods of tag SNPs and candidate SNPs. The associations between eleven SCN11A SNPs and basic pain sensitivity in female healthy volunteers were analyzed using the Plink software. The SNPs associated with basic pain sensitivity were termed positive SCN11A SNPs. The effect of these positive SNPs on postoperative pain sensitivity was explored in patients undergoing elective gynecological laparoscopic surgery and receiving postoperative patient-controlled analgesia (PCA). We assessed pain intensity using the numeric pain rating scale (NRS) and recorded PCA consumption.Our results suggested that 5 SNPs (rs33985936, rs13080116, rs11720988, rs11709492, and rs11720013) in 11 tag and candidate SNPs were associated with basic pain sensitivity (P < .05). No evident association was found between the 5 positive SNPs and NRS (P > .05). However, among these positive SNPs, the minor alleles of rs33985936 and rs13080116 were significantly associated with increased PCA consumption (P < .01).To our knowledge, this is the first study to report that SCN11A SNPs affect postoperative pain sensitivity in Chinese Han women after gynecological surgery. The SNP rs33985936 and rs13080116 may serve as novel predictors for postoperative pain.

Anesthetic management during adenotonsillectomy for twins with congenital insensitivity to pain with anhidrosis: two case reports.

BACKGROUND: Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder characterized by hyperpyrexia, anhidrosis, pain insensitivity, self-inflicted injuries, and intellectual disability. The anesthetic management of these patients is challenging owing to the high risk of perioperative complications resulting from their autonomic dysfunction, such as hyperthermia, hypotension, and bradycardia, which result from autonomic nervous system dysfunction. CASE PRESENTATION: Two 3-year-old Han Chinese identical male twins (weighing 13.5 kg and measuring 93 cm tall) were previously diagnosed as having congenital insensitivity to pain with anhidrosis based on clinical features and genetic screening. According to the presence of loud snoring and heavy breathing during sleep and neck radiograph findings, they were diagnosed as having tonsil and adenoid hypertrophy and needed adenotonsillectomy. Because of innate analgesia, some reports suggested that patients with congenital insensitivity to pain with anhidrosis do not require perioperative pain control. Accordingly, our patients did not receive opiates. We describe the general anesthetic management of these patients using sevoflurane and propofol, but without opiates, for adenotonsillectomy. Remarkable tachycardia and hypertension occurred during airway manipulation and when the surgical stimuli increased, and their temperatures increased from 36 °C and 36.8 °C to 37.8 °C and 38.5 °C, respectively. Patients with congenital insensitivity to pain with anhidrosis lack pain sensation, but they may have tactile hyperesthesia. Surgical noxious stimuli may therefore produce a stress response and unpleasant sensations, leading to hemodynamic fluctuation and temperature increase. CONCLUSIONS: On the basis of these findings, we suggest that careful intraoperative opiate titration may be justified to blunt the surgical stress response and promote hemodynamic and temperature stability in similar patients; we also recommend the preparation of warming and cooling devices and continuous temperature monitoring in these patients. Since anesthetic management of these patients is not simple, careful attention is required.

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.

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.

Novel and novel de novo mutations in NTRK1 associated with congenital insensitivity to pain with anhidrosis: a case report.

Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare autosomal recessively inherited disorder. The main clinical features of the disorder consist of absence of reactions to noxious stimuli and inability to sweat under any conditions.In this case report, a 3-year-old Chinese boy diagnosed with CIPA presented with the core features of CIPA, including insensitivity to noxious stimuli, self-mutilation, inability to sweat, and developmental delay. Clinical and genetic analyses were conducted on the affected boy.Sequencing analysis revealed an inherited novel mutation, c.1635G>C, and a novel de novo mutation, c.2197G>A, in the NTRK1 gene. In silico studies suggested that the mutations described are detrimental to the function of the protein encoded by the NTRK1 gene.The two novel mutations described here widen the genetic spectrum of CIPA, and this knowledge will benefit studies addressing this disease and pain medicine in the future.

[Comparison of sufentanil-tramadol PCIA between laparoscopic cholecystectomy and gynecological laparoscopy].

OBJECTIVE: To compare the differences of postoperative patient-controlled intravenous analgesia for laparoscopic cholecystectomy and gynecological laparoscopy in female patients. METHODS: This retrospective study included 645 female patients received laparoscopic cholecystectomy or gynecological laparoscopy (laparoscopic oophorocystectomy/myomectomy) between January 2011 and July 2012 in Tongji Hospital. Among them, 207 cases of sufentanil-tramadol patient-controlled intravenous analgesia (PCIA) were enrolled and divided into 2 groups:77 cases in laparoscopic cholecystectomy group, and 130 cases in gynecological laparoscopy group. The pressing frequency and consumption of PCIA, localization and quality of postoperative pain, visual analogue scale (VAS) at 4-6 h, 8-12 h, 18-24 h after surgery, and adverse effect were compared by t-test,χ(2) test, Fisher exact test or Mann-Whitney test. RESULTS: There was no statistical difference of age, body mass index, and operation time between the two groups (all P > 0.05). As compared with the gynecological laparoscopy group (3 (4)), PCIA pressing frequency was higher in the laparoscopic cholecystectomy group (5 (7)), but there was no statistical difference (Z = -1.747, P = 0.081). PCIA consumption in the laparoscopic cholecystectomy group (79 (33) ml) was higher than that in the gynecological laparoscopy group (48 (30) ml) (Z = -6.267, P = 0.000). The postoperative pain localization and quality were different in the two groups, the patients in the laparoscopic cholecystectomy group experienced dull pain in lower abdomen, but the ones in the gynecological laparoscopy group had distending pain in upper abdomen and piercing pain around scapula. The differences of 4-6 h, 8-12 h, 18-24 h VAS scores in the two groups had no statistical significance (all P > 0.05). The total incidence of postoperative adverse effect between the two groups had no statistical significant difference (laparoscopic cholecystectomy group:11.7%, gynecological laparoscopy group:16.2%) (χ(2) = 0.778, P = 0.378). The incidence of dizziness was higher in the gynecological laparoscopy group (6.2%) than that in the laparoscopic cholecystectomy group (0) (Fisher exact test:P < 0.05). CONCLUSION: In the case of sufentanil-tramadol PCIA, laparoscopic cholecystectomy needs more postoperative analgesia, while gynecological laparoscopy has higher incidence of dizziness.

A new real-time method for detecting the effect of fentanyl using the preoperative pressure pain threshold and Narcotrend index: a randomized study in female surgery patients.

Individual variability in the effects of opioid analgesics such as fentanyl remains a major challenge for tailored pharmacological treatment including postoperative analgesia. This study aimed to establish a new real-time method for detecting the effects of fentanyl and their individual differences in the preoperative period, using the pressure pain threshold (PPT) and Narcotrend index (NTI) test.Eighty women undergoing elective surgery under general anesthesia were enrolled in this randomized, double-blinded, placebo-controlled study to receive either intravenous fentanyl (Group F) or saline (Group S). Before (T1) and 5 (T2) and 10 min (T3) after intravenous injection, the PPT, NTI, respiratory rate, heart rate, blood pressure, and pulse oxygen saturation were measured. The initial time at which the Narcotrend index showed a decline was also recorded.In total, 40 patients in Group S and 38 patients in Group F were included in the final analysis. At 5 min and 10 min after intravenous fentanyl administration, the analgesic effect was determined by measuring the PPT, which was significantly increased (P < 0.001), and the sedative effect was detected using the NTI, which was significantly decreased (P < 0.001). The distribution of percentage changes of the PPT and NTI showed individual differences. At T2 and T3, the absolute changes in NTI and PPT were positively correlated (r = 0.444 at T2, P = 0.005; r = 0.332 at T3, P = 0.042).Through the PPT and NTI, it was feasible to easily detect the effects of fentanyl and their individual differences in real time before induction of anesthesia in the operation room. This method could potentially be applied to preoperatively determine patients' sensitivity to fentanyl.

An improvement of mechanical pain sensitivity measurement method: the smaller sized probes may detect heterogeneous sensory threshold in healthy male subjects.

OBJECTIVE: On the basis of our experience in the application of the mechanical algometer and a number of pilot experiments, we speculated that 0.1- and 0.01-cm(2) probes might improve the measurement of mechanical pain sensitivity relative to the conventional 1-cm(2) probe. Here, we examined the accuracy, feasibility, and applicability of these probes in detecting the mechanical pain sensitivity. DESIGN: Mechanical pain threshold and tolerance tests were performed on subjects using the three probes of 1, 0.1, and 0.01 cm(2) in random order. We compared the application of these probes. SETTING: The study was set at the Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. SUBJECTS: Fifty healthy male Han Chinese subjects were recruited. OUTCOME MEASURES: We compared the qualities of stimulus-evoked pain, test stability, the measuring time, the subjects' acceptance level of the procedure, the validity of pain measurement, and the arduousness of the task for the investigator among the three different size probes. RESULTS: Compared with the conventional 1-cm(2) probe, the 0.01- and 0.1-cm(2) probes resulted in the subjects responding to stimulus-evoked pain more quickly, accurately, and consistently, and also made the measurement more comfortable for investigators. Up to 80% of the subjects reported the pain quality as a pricking sensation when the 0.01-cm(2) probe was used. CONCLUSION: The use of the 0.1-cm(2) probe might be more suitable as an optimized method for the detection of pressure pain sensitivity in clinical studies. In addition, the 0.01-cm(2) probe could potentially serve as an alternative to the weighted needle pinprick, providing continuous quantizing detection for pricking pain sensitivity.