Spinal MCP-1 Contributes to Central Post-stroke Pain by Inducing Central Sensitization in Rats.

Central post-stroke pain (CPSP) is a highly refractory form of central neuropathic pain that has been poorly studied mechanistically. Recent observations have emphasized the critical role of the spinal dorsal horn in CPSP. However, the underlying mechanisms remain unclear. In this study, rats were subjected to thalamic hemorrhage to investigate the role of spinal monocyte chemoattractant protein-1 (MCP-1) and C-C motif chemokine receptor 2 (CCR2) in the development of CPSP. Immunohistochemical staining and ELISA were used to assess the expression changes of c-Fos, Iba-1, GFAP, MCP-1, and CCR2 in the dorsal horn of the lumbar spinal cord following thalamic hemorrhage, and the involvement of spinal MCP-1 in CPSP was examined by performing intrathecal anti-MCP-1 mAb injection to neutralize the spinal extracellular MCP-1. We demonstrated that intra-thalamic collagenase microinjection induced persistent bilateral mechanical pain hypersensitivity and facilitated the spontaneous pain behaviors evoked by intraplantar bee venom injection. Accompanying CPSP, the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn was significantly increased up to 28 days post-intra-thalamic collagenase microinjection. Intrathecal injection of minocycline and fluorocitrate dramatically reverses the bilateral mechanical pain hypersensitivity. Moreover, intra-thalamic collagenase microinjection dramatically induced the up-regulation of MCP-1 but had no effect on the expression of CCR2 in the bilateral lumbar spinal dorsal horn, and MCP-1 was primarily localized in the neuron. Intrathecal injection of anti-MCP-1 mAb was also able to reverse CPSP and reduce the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn. These findings indicated that spinal MCP-1 contributes to CPSP by mediating the activation of spinal neurons and glial cells following thalamic hemorrhage stroke, which may provide insights into pharmacologic treatment for CPSP.

Ropivacaine-induced seizures evoked pain sensitization in rats: Participation of 5-HT/5-HT3R.

Due to the increasing use of local anesthetic techniques in various healthcare settings, local anesthetic toxicity still occurs. Seizures are the most common symptom of local anesthetic toxicity. The relationship between local anesthetic-induced seizures and the sensation of pain has not been established till now. Here, we assessed the development of pain hypersensitivity after ropivacaine-induced seizures (RIS) and the influence of RIS on incision-induced postsurgical pain and formalin-induced acute inflammatory pain. In addition, the involvement of spinal 5-HT/5-HT3R in RIS-induced pain sensitization was investigated. According to a sequential exploratory experimental strategy, we first calculated the 50% seizure dosage of ropivacaine to be 42.66 mg/kg (95% confidence interval: 40.19-45.28 mg/kg). We showed that RIS induced significant bilateral mechanical pain hypersensitivity that lasted around 5 days, accompanied by an increase in spinal 5-HT. Moreover, RIS considerably protracted postsurgical pain and enhanced formalin-induced spontaneous flinching in the second phase. Depletion of spinal 5-HT with intrathecal injection of 5,7-dihydroxytryptamine (5,7-DHT) reduced RIS-induced pain hypersensitivity and prevented the prolonging of postsurgical pain following RIS. Likewise, blocking spinal 5-HT3R by intrathecal administration of ondansetron reversed RIS-induced pain hypersensitivity and attenuated the pronociception of RIS in the formalin test. Our findings revealed that acute RIS led to pain hypersensitivity and had pronociceptive effects on incision-induced postsurgical pain and formalin-induced acute inflammatory pain. Moreover, our data implied that RIS-induced pain sensitization depends on spinal 5-HT/5-HT3R signaling. Thus, targeting the descending serotonergic facilitation system should be an important element of the precise treatment for local anesthetic toxicity.

A 10-Year Prevalence Survey and Clinical Features Analysis of Pressure Injury in a Tertiary Hospital in China, 2009-2018.

OBJECTIVE: To describe the 10-year prevalence of pressure injury (PI) in a tertiary hospital in China and determine the clinical characteristics of inpatients with PI. METHODS: The authors performed a retrospective analysis of PI cases extracted from the electronic health record of a tertiary hospital. The trend of PI prevalence over 10 years was described by estimating the average percent change (EAPC). Comorbidities were described with the Charlson Comorbidity Index (CCI). The clinical characteristics of PI were described using the number of cases and composition ratio. RESULTS: The overall prevalence of PI was 0.59% (5,838/986,404). From 2009 to 2018, the rate increased from 0.19% to 1.00% (EAPC = 22.46%). When stage I PIs were excluded, the prevalence of PI ranged from 0.15% to 0.79% (EAPC = 21.90%). The prevalence of hospital-acquired PI was 0.13%. Prevalence increased with age (Ptrend < .001) and was significantly higher in men than women (P < .001). Patients with PI were more widely distributed in the ICU (20.58%), vasculocardiology department (11.73%), gastroenterology department (10.18%), and OR (8.29%). Of patients with PI, 71.3% had a CCI score 4 or higher. CONCLUSIONS: The PI prevalence in the study facility increased rapidly over the study period. Pressure injuries among patients in the gastroenterology department and in the community deserve more attention. The CCI may be a good indicator for PI risk assessment.

Identification of aberrantly expressed circular RNAs in hyperlipidemia-induced retinal vascular dysfunction in mice.

Hyperlipidemia-induced retinal vascular dysfunction is a complex pathological process. circRNAs are important regulators of biological processes and disease progression. However, the expression pattern of circRNAs in hyperlipidemia-induced retinal vascular dysfunction remains unclear. Herein, we used a murine model of hyperlipidemia and identified 317 differentially expressed circRNAs between hyperlipidemic retinas and normolipidemic retinas by circRNA microarrays. GO analysis indicated that the host genes of dysregulated circRNAs were targeted to cell differentiation (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis revealed that circRNAs-mediated network was mostly enriched in focal adhesion signaling. Notably, circLDB1 was significantly up-regulated in the serum of coronary artery disease patients and aqueous humor of age-related macular degeneration patients. circLDB1 regulated endothelial cell viability, proliferation, and apoptosis in vitro. Thus, circRNAs are the promising targets for the prediction and diagnosis of hyperlipidemia-induced vascular diseases.

CYP24A1 genetic variants in the vitamin D metabolic pathway are involved in the outcomes of hepatitis C virus infection among high-risk Chinese population.

BACKGROUND AND AIMS: It has been demonstrated that 1,25-hydroxyvitamin-D3-24-hydroxylase, encoded by CYP24A1 gene, is a key enzyme that neutralizes the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in response to hepatitis C virus (HCV) infection. This study aimed to investigate whether CYP24A1 genetic variation is associated with HCV infection outcomes. METHODS: 848 HCV chronically infected subjects, 507 natural clearance subjects, and 1017 uninfected controls were enrolled. Nine single nucleotide polymorphisms (SNPs) in theCYP24A1 gene were genotyped using the Sequenom MassARRAY platform. RESULTS: After adjusting for age, gender, and routes of infection, logistic regression analyses showed that rs6013897-A was associated with an elevated risk of HCV infection (P<0.05). In addition, this study has also demonstrated that rs6068816-T significantly reduced the risk of chronic HCV infection, while rs3787557-C, rs6022999-G, and rs2248359-T significantly increased the risk of chronic HCV infection (all P<0.05). Haplotype analysis suggested that, compared to the most frequent Trs6068816Trs3787557Ars6022999Crs2248359 haplotype, the CTGT haplotype (adjusted OR=1.376, 95% CI=1.092-1.735, P=0.007) and CCAC haplotype (adjusted OR=1.483, 95% CI=1.139-1.929, P=0.003) were associated with an increased risk of chronic HCV infection. CONCLUSION: These findings indicate that SNPs in CYP24A1 gene may contribute to the risk of HCV infection and chronic HCV infection among a high-risk Chinese population.