minocycline and Pancreatitis--Chronic

The chronic, persistent pain associated with chronic pancreatitis (CP) has many characteristics of neuropathic pain, initiated and maintained by the activation of spinal microglia. We investigated whether activated microglia in the thoracic spinal cord contribute to chronic pain in a rat model of CP.. CP was induced in Sprague-Dawley rats by an intraductal injection of 2% trinitrobenzene sulfonic acid. Hyperalgesia was assessed by the measurement of mechanical sensitivity of the abdomen and nocifensive behavior to electrical stimulation of the pancreas. Three weeks after induction of CP, spinal samples were analyzed by immunostaining and immunoblot analyses for levels of CD11 (a marker of microglia, determined with the antibody OX42) and phosphorylated p38 (P-p38, a marker of activation of p38 mitogen-activated protein kinase signaling). We examined the effects of minocycline (inhibitor of microglia) and fractalkine (microglia-activating factor) on visceral hyperalgesia in rats with CP.. Rats with CP had increased sensitivity and nociceptive behaviors to mechanical probing of the abdomen and electrical stimulation of the pancreas. The dorsal horn of the thoracic spinal cords of rats with CP contained activated microglia (based on increased staining with OX42), with an ameboid appearance. Levels of P-p38 increased in rats with CP and colocalized with OX42-positive cells. Intrathecal injection of minocycline reversed and prevented the increase of nocifensive behaviors and levels of P-p38 in rats with CP. Fractalkine induced hyperalgesia in rats without CP, which was blocked by minocycline.. Activated spinal microglia have important roles in maintaining and initiating chronic pain in a rat model of CP. Microglia might be a target for treatment of hyperalgesia caused by pancreatic inflammation.

Topics: Animals; Blotting, Western; CD11 Antigens; Chemokine CX3CL1; Disease Models, Animal; Enzyme Activation; Hyperalgesia; Immunohistochemistry; Male; Microglia; Minocycline; p38 Mitogen-Activated Protein Kinases; Pain Measurement; Pain Threshold; Pancreatitis, Chronic; Phosphorylation; Rats; Rats, Sprague-Dawley; Spinal Cord; Thoracic Vertebrae; Time Factors; Trinitrobenzenesulfonic Acid

Knowledge of the etiology of pyogenic liver and pancreatic abscesses is an important factor in determining the success of combined surgical and antibiotic treatment. Literature shows geographical variations in the prevalence and distribution of causative organisms, and the spread of Klebsiella pneumoniae carbapenemase-producing bacteria is an emerging cause of abdominal infections.. We herein describe two cases of intra-abdominal abscesses due to monomicrobial infection by Klebsiella pneumoniae Sequence Type 258 producing K. pneumoniae carbapenemase 3 (KPC-Kp). In case 1, a 50-year-old HIV-negative Italian woman with chronic pancreatitis showed infection of a pancreatic pseudocystic lesion caused by KPC-Kp. In case 2, a 64-year-old HIV-negative Italian woman with pancreatic neoplasm and liver metastases developed a liver abscess due to KPC after surgery. Both women were admitted to our hospital but to different surgical units. The clonal relationship between the two isolates was investigated by pulsed-field gel electrophoresis (PFGE). In case 2, the patient was already colonized at admission and inter-hospital transmission of the pathogen was presumed. A long-term combination regimen of colistin with tigecycline and percutaneous drainage resulted in full recovery and clearance of the multidrug-resistant (MDR) pathogen.. Timely microbiological diagnosis, the combined use of new and old antibiotics and radiological intervention appeared to be valuable in managing these serious conditions. The emergence and dissemination of MDR organisms is posing an increasing challenge for physicians to develop new therapeutic strategies and control and prevention frameworks.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Neoplasms; Middle Aged; Minocycline; Pancreatic Neoplasms; Pancreatitis, Chronic; Tigecycline