Genetic liability to multi-site chronic pain increases the risk of cardiovascular disease.

BACKGROUND: Observational studies have shown associations between multi-site chronic pain (MCP) and cardiovascular disease. However, it remains unclear whether these associations are causal. Therefore, this study aimed to assess the causal associations between MCP and cardiovascular disease and identify possible mediators between them. METHODS: A two-sample Mendelian randomisation analysis was applied in this study. The summary data for MCP were obtained from a genome-wide association study that included 387 649 individuals from the UK Biobank, whereas summary-level data for cardiovascular disease and its subtypes were obtained from relevant genome-wide association studies. Finally, summary-level data for common cardiovascular risk factors and inflammatory biomarkers were leveraged to identify possible mediators. RESULTS: Genetic liability to multi-site chronic pain is associated with higher risks for coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), and stroke, with a combined odds ratio (OR) of 1.537 (per site increment in MCP; 95% confidence interval [CI]: 1.271-1.858; P=0.0001) for CAD, 1.604 (95% CI: 1.277-2.014; P=0.0005) for MI, 1.722 (95% CI: 1.423-2.083; P<0.00001) for HF, and 1.332 (95% CI: 1.093-1.623; P=0.00001) for stroke. Genetic liability to MCP was found to be associated with mental disorders, smoking initiation, physical activity, BMI, and lipid metabolites. Multivariable Mendelian randomisation suggested a mediating role for mental disorders, smoking initiation, physical activity, and BMI in the relationship between multi-site chronic pain and cardiovascular disease. CONCLUSIONS: Our findings provide new insights into the role of multi-site chronic pain in cardiovascular disease. Additionally, we identified several modifiable risk factors for reducing cardiovascular disease.

Gut microbiota alterations may increase the risk of prescription opioid use, but not vice versa: A two-sample bi-directional Mendelian randomization study.

Introduction: Gut microbiota alterations are strongly associated with prescription opioid use (POU) and multisite chronic pain (MCP). However, whether or not these associations are causal remains unknown. Therefore, we aim to explore the causal relationships between them comprehensively. Methods: A two-sample bi-directional Mendelian randomization was conducted to assess the potential associations between gut microbiota and POU/MCP using summary level Genome-wide association studies (GWASs) that were based on predominantly European ancestry. Results: Potential causal effects were identified between seven host genetic-driven traits of gut microbiota on POU, including Adlercreutzia, Allisonella, Dialister, Anaerofilum, Anaerostipes, ChristensenellaceaeR.7group, and LachnospiraceaeNC2004group at the genus level (p < 0.05) by the Inverse-variance weighted method, with significant causal effects of ChristensenellaceaeR.7group and Allisonella on POU (p < 0.025). A total of five genetically greater abundance of gut microbiota traits were identified to be possibly related to the level of MCP (p < 0.05), including genus ErysipelotrichaceaeUCG003, family Clostridiaceae1, order Gastranaerophilales, order Actinomycetales, and family Actinomycetaceae. In the other direction, no clear evidence was found to support a significant causal relationship between POU and gut microbiota, as well as MCP and gut microbiota. In addition, evidence was also provided for the relationship between triacylglycerols and diacylglycerol elevation, and an increased risk of POU and MCP. No evidence was found across various sensitivity analyses, including reverse causality, pleiotropy, and heterogeneity. Conclusion: The findings from this study provide robust evidence that gut microbiota alterations may be a risk of POU/MCP, but not vice versa.

Celiac plexus block for treatment of pain associated with pancreatic cancer: a meta-analysis.

Pancreatic ductal adenocarcinoma has a high rate of neural invasion (80 to 100%) and can be associated with moderate to severe pain in pancreatic cancer. Treatment of pain with celiac plexus blockage (CPB) combined with the three-step ladder utilization of pharmaceutical analgesics following WHO guidelines is used, but the evidence in randomized controlled trials is inconsistent. This meta-analysis identified and compared seven randomized control trials of pain relief from pancreatic cancer, by treatment with medical management alone to celiac plexus blockade with medical management. While no evidence of potential publication bias was detected, group size and statistical power may account for some of the inconsistent conclusions. The combined CPB groups had a significantly lower pain score at 4 weeks, but significance was not maintained at 8 weeks. The combined CPB groups required significantly less drug use compared to the combined control groups treated with pharmaceutical analgesics.

[Effect of dexmedetomidine in preventing shivering after general anesthesia for laparoscopic surgery: a randomized, single-blinded, and placebo-controlled trial].

OBJECTIVE: To evaluate efficacy of dexmedetomidine in preventing shivering after general anesthesia in women undergoing laparoscopic surgery. METHODS: Eighty patients scheduled for laparoscopic gynecological surgery were randomized into dexmedetomidine group (n=40) and control group (n=40) to receive 1.0 µg/kg dexmedetomidine or an equal volume of saline slowly injected (for over 10 min) at 30 min before the anticipated completion of surgery. The postoperative incidences of shivering and the side effects were recorded. RESULTS: The patients in the control group showed a significantly higher postoperative incidence of shivering (37.5%) than those in dexmedetomidine group (P<0.05). Heart rate and mean arterial pressure showed significant variations postoperatively in dexmedetomidine group (P<0.05), which had a significantly greater sedation score (P<0.05), a higher incidence of dry mouth (P=0.000), but a significantly lower incidence of nausea and vomiting than the control group (P<0.05). CONCLUSION: Dexmedetomidine can lower the incidence of shivering after general anesthesia for laparoscopic gynecological surgery.

In vitro and in vivo effects of ketamine on generation and function of dendritic cells.

The question about how intravenous anesthetic reagents affect the development and function of dendritic cell subsets still has no comprehensive answers. Bone marrow cells differentiated with FMS-like tyrosine kinase 3 ligand in vitro represented the steady-state dendritic cell subsets. The effects of ketamine on the generation and function of dendritic cell subsets were investigated. We found that dendritic cell subsets responded to the anesthetic reagent ketamine in several aspects: 1) The in vitro and in vivo development of plasmacytoid dendritic cells were inhibited by ketamine at high concentrations; 2) The endocytosis of dendritic cells were not influenced by ketamine at concentrations from 50 - 200 µM; 3) The maturation markers of conventional dendritic cells were not changed by ketamine upon LPS or CpG stimulation, although the cytokines mRNA profiles were affected; 4) The allogenic-stimulatory activity of dendritic cells was suppressed by ketamine. In conclusion, ketamine hampered plasmacytoid dendritic cell subset development both in vivo and in vitro. The dendritic cells maturation and downstream responses towards different toll-like receptor stimuli were differently regulated by ketamine treatment.