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 À4.3 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.

Patients carrying the SCN9A 3312Tallele presented with lower postoperative pain sensitivity in the presence of a similar surgical pain stimulus, and had a lower likelihood of developing inadequate analgesia than those carrying the 3312Gallele.

ObjectiveNeurological dysfunction remains a devastating postoperative complication in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), and previous studies have shown that inhalation anaesthesia and total intravenous anaesthesia (TIVA) may produce different degrees of cerebral protection in these patients. Therefore, we conducted a systematic literature review and meta-analysis to compare the neuroprotective effects of inhalation anaesthesia and TIVA.DesignSearching in PubMed, EMBASE, Science Direct/Elsevier, China National Knowledge Infrastructure and Cochrane Library up to August 2016, we selected related randomised controlled trials for this meta-analysis.ResultsA total of 1485 studies were identified. After eliminating duplicate articles and screening titles and abstracts, 445 studies were potentially eligible. After applying exclusion criteria (full texts reported as abstracts, review article, no control case, lack of outcome data and so on), 13 studies were selected for review. Our results demonstrated that the primary outcome related to S100B level in the inhalation anaesthesia group was significantly lower than in the TIVA group after CPB and 24 hours postoperatively (weighted mean difference (WMD); 95% CI (CI): −0.41(–0.81 to –0.01), −0.32 (−0.59 to −0.05), respectively). Among secondary outcome variables, mini-mental state examination scores of the inhalation anaesthesia group were significantly higher than those of the TIVA group 24 hours after operation (WMD (95% CI): 1.87 (0.82 to 2.92)), but no significant difference was found in arteriovenous oxygen content difference, cerebral oxygen extraction ratio and jugular bulb venous oxygen saturation, which were assessed at cooling and rewarming during CPB.ConclusionThis study demonstrates that anaesthesia with volatile agents appears to provide better cerebral protection than TIVA for patients undergoing cardiac surgery with CPB, suggesting that inhalation anaesthesia may be more suitable for patients undergoing cardiac surgery.

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.

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.

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The study aimed to investigate the effects of intraoperative dexmedetomidine on postoperative sleep disturbance for different surgical patients and compare such effects between different dose of dexmedetomidine. Methods: A total of 7418 patients undergoing nine types of non-cardiac major surgeries were retrospectively studied. Patients were separated into DEX (dexmedetomidine) or Non-DEX (Non-dexmedetomidine) groups based on the use of dexmedetomidine during surgery. The patients who reported they could not fall asleep during the night or woke up repeatedly during the most of the night at the day of the surgery and whose NRS were >6 were defined as cases with severe sleep disturbance. Propensity score matched analysis based on all preoperative baseline data was performed along with logistic regression analysis including different surgery types and dosage of dexmedetomidine use. Results: In both of the unmatched cohort (OR, 0.49 [95% CI: 0.43-0.56]) and matched cohort (0.49 [95% CI: 0.42-0.58]), the DEX group had a significantly lower incidence of severe sleep disturbance than the Non-DEX group. In the subgroup analysis, for gynecological and urological surgery population, the ORs for DEX-group reached 0.21 (95% CI, 0.13-0.33; P<0.0001) and 0.30 (95% CI,0.19-0.47; P<0.0001), respectively. In addition, low-dose dexmedetomidine (0.2-0.4 μg•kg −1 •h −1) showed the greatest effect with an odds ratio of 0.38 (95% CI: 0.31-0.44; P<0.0001), and the incidence of severe sleep disturbance in the low-dose group was significantly lower (11.5% vs. 17.7% vs. 16.5%, P<0.0001) than that in the medium-(0.4-0.6 μg•kg −1 •h −1) and high-dose (0.6-0.8 μg•kg −1 •h −1) groups. Conclusion: Intraoperative dexmedetomidine use can significantly decrease the incidence of severe sleep disturbance on the day of surgery for patients undergoing non-cardiac major surgery, and the effects were most significant in patients receiving gynecological and urological surgery. Furthermore, low-dose dexmedetomidine (0.2-0.4 μg•kg −1 •h −1) is most effective for prevention of postoperative sleep disturbance.

ObjectiveTo compare the analgesic effects of patient-controlled intravenous analgesia (PCA) with hydromorphone and sufentanil after thoracic surgery on postoperative pulmonary complications (PPCs).MethodsA total of 142 patients who were scheduled for thoracic surgery were randomly allocated to receive PCA with hydromorphone (group A: experimental group): hydromorphone 0.2 mg/kg + dezocine 0.5 mg/kg + ramosetron 0.6 mg diluted with normal saline to 200 mL; or with sufentanil (group B: control group): sufentanil 3.0μg/kg + dezocine 0.5 mg/kg + ramosetron 0.6 mg diluted with normal saline to 200 mL. The parameters of intravenous analgesia pump were set as background dose 4 ml/h, PCA dose 1 mL, locking time 15 min. Pain NRS (numerical rating scale), Ramsay sedation score, nausea or vomiting score were evaluated at 0 h, 6 h, 12 h, 24 h, 48 h after operation. The cases of PPCs (atelectasis, pulmonary infection, respiratory failure), CRP (C-reaction protein) and inflammatory cells (white cell count and percentage of neutrophils) and blood gas analysis at 12 h after operation, length of ICU and postoperative stay were recorded for each patient.ResultsData of 136 patients were analyzed. Compared with group B (4[IQR:2,2]), the pain NRS in group A (2[IQR:4,4]) was significantly lower at 6 h after operation (P = 0.000). The CRP in group A (69.79 ± 32.13 mg/L) were lower than group B (76.76 ± 43.42 mg/L) after operation, but the difference was not significant (P = 0.427). No difference of nausea or vomiting was found between group A (7.3%) and group B (5.8%) postoperatively (P = 0.999). The PPCs were happened in 11 patients in group A (16.2%) and 22 patients in group B (32.4%) and the difference between two groups was significant (P = 0.027). Seven patients in group A (10.3%) and eighteen patients in group B (26.5%) had clinical evidence of pneumonia and the difference between two groups was significant (P = 0.014). The length of ICU and postoperative stay in group A were 2.73 h and 1.82 days less than group B respectively but the differences were not significant (P = 0.234, P = 0.186 respectively).ConclusionCompared with sufentanil, hydromorphone may provide better postoperative analgesic effect with less pulmonary complications for patients undergoing thoracic surgery, and it may accelerate patients’ rehabilitation.Trial registrationRandomized Controlled Trials ChiCTR1800014282c. Registered 3 January 2018.