[Chronic liver disease increases with damage to intestinal barrier function].

Objective: To probe into the correlation between chronic liver disease and intestinal barrier function. Methods: 1 491 cases of hospitalized patients were enrolled, of which 741 cases were of chronic liver diseases, including 397 cases of fatty liver diseases, 230 cases of chronic hepatitis, 114 cases of liver cirrhosis, and 750 cases of non-hepatic diseases. All admitted patients' intestinal barrier function like diamine oxidase (DAO), D-lactate, lipopolysaccharide, and biochemical indicators of liver functions were tested. According to different data, statistical analysis was done using t-test, ANOVA, Dunnett's test, χ (2) test of fourfold table, Pearson's correlation, and binary logistic regression. Results: The intestinal barrier dysfunction was more likely to occur in the chronic liver disease group than that of non-hepatic disease group [54.15% (379/741) vs. 18.53% (139/750), χ (2) = 193.58, P < 0.001]. The correlation analysis between biochemical indicators of liver function and intestinal barrier function in chronic liver disease group showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and total bilirubin levels were more susceptible to intestinal barrier dysfunction than those with normal indexes (P < 0.05 ). GGT had stimulated DAO (P < 0.05, OR > 1), D-lactate (P < 0.05, OR > 1), lipopolysaccharide (P < 0.05, OR > 1), ALT and AST. Conclusion: Chronic liver disease increases with damage to intestinal barrier function.

Robust increase of cutaneous sensitivity, cytokine production and sympathetic sprouting in rats with localized inflammatory irritation of the spinal ganglia.

We investigated the role and mechanisms of inflammatory responses within the dorsal root ganglion (DRG) in the development of chemogenic pathological pain. DRG inflammation was induced by a single deposit of the immune activator zymosan in incomplete Freund's adjuvant in the epidural space near the L5 DRG via a small hole drilled through the transverse process. After a single zymosan injection, rats developed bilateral mechanical hyperalgesia and allodynia which began by day 1 after surgery, peaked at days 3-7, and lasted up to 28 days. The number of macrophages in ipsilateral and contralateral DRGs increased significantly, lasting over 14 days. Robust glial activation was observed in inflamed ganglia. Cytokine profile analysis using a multiplexing protein array system showed that, in normal DRG, all but interleukin (IL)-5, IL-10 and granulocyte-macrophage colony stimulating factor (GM-CSF) were detectable with concentrations of up to 180 pg/mg protein. Local inflammatory irritation selectively increased IL-1beta, IL-6, IL-18, monocyte chemoattractant protein-1 (MCP-1), and growth-related oncogene (GRO/KC) up to 17-fold, and decreased IL-2 and IL-12 (p70) up to threefold. Inflaming the DRG also remarkably increased the incidence of spontaneous activity of A- and C-fibers recorded in the dorsal root. Many of the spontaneously active A-fibers exhibited a short-bursting discharge pattern. Changes in cytokines and spontaneous activity correlated with the time course of pain behaviors, especially light stroke-evoked tactile allodynia. Finally, local inflammation induced extensive sprouting of sympathetic fibers, extending from vascular processes within the inflamed DRG. These results demonstrate the feasibility of inducing chronic localized inflammatory responses in the DRG in the absence of traumatic nerve damage, and highlight the possible contribution of several inflammatory cytokines/chemokines to the generation of spontaneous activity and development and persistence of chemogenic pathologic pain.