Current Approaches to Four Challenging Pain Syndromes.

During a conference of pain specialists, some of the experts addressed the potential management of four prevalent but difficult painful conditions, namely, chronic postsurgical pain (CPSP), knee osteoarthritis, chest trauma, and facet joint arthropathy. In all cases, the conditions posed challenges in accurate diagnoses as well as safe, effective treatments, especially using locoregional blocks. It is not clear why some surgical patients develop CPSP and others do not, although some risk factors have been identified. More importantly, the transitional phase of pain from acute to chronic deserves greater scrutiny. It appears as if more aggressive and more effective perioperative and postoperative analgesia could help mitigate or possibly prevent CPSP. Knee osteoarthritis is prevalent but is often managed pharmacologically and then with joint replacement; many patients simply live with the condition which can be viewed as a disease of the entire joint. New approaches with intra-articular injections of hyaluronic acid, platelet-rich plasma, and botulinum toxin may provide safe, effective, and durable pain control. Chest trauma can be extremely painful and a source of morbidity, but its management tends to rely on watchful waiting and drug therapy. New approaches to regional nerve blocks can be beneficial and may reduce troublesome symptoms such as the inability to cough or clear the lungs. Facet joint arthropathy is very prevalent among older people but is not completely clarified. It may be the source of intense pain with limited management strategies. The role of nerve blocks in facet joint arthropathy is an important new addition to the armamentarium of pain management, particularly for geriatric patients.

Deficiency of liver adipose triglyceride lipase in mice causes progressive hepatic steatosis.

UNLABELLED: Accumulation of cytoplasmic triacylglycerol (TG) underlies hepatic steatosis, a major cause of cirrhosis. The pathways of cytoplasmic TG metabolism are not well known in hepatocytes, but evidence suggests an important role in lipolysis for adipose triglyceride lipase (ATGL). We created mice with liver-specific inactivation of Pnpla2, the ATGL gene. These ATGLLKO mice had severe progressive periportal macrovesicular and pericentral microvesicular hepatic steatosis (73, 150, and 226 µmol TG/g liver at 4, 8, and 12 months, respectively). However, plasma levels of glucose, TG, and cholesterol were similar to those of controls. Fasting 3-hydroxybutyrate level was normal, but in thin sections of liver, beta oxidation of palmitate was decreased by one-third in ATGLLKO mice compared with controls. Tests of very low-density lipoprotein production, glucose, and insulin tolerance and gluconeogenesis from pyruvate were normal. Plasma alanine aminotransferase levels were elevated in ATGLLKO mice, but histological estimates of inflammation and fibrosis and messenger RNA (mRNA) levels of tumor necrosis factor-α and interleukin-6 were similar to or lower than those in controls. ATGLLKO cholangiocytes also showed cytoplasmic lipid droplets, demonstrating that ATGL is also a major lipase in cholangiocytes. There was a 50-fold reduction of hepatic diacylglycerol acyltransferase 2 mRNA level and a 2.7-fold increase of lipolysosomes in hepatocytes (P < 0.001), suggesting reduced TG synthesis and increased lysosomal degradation of TG as potential compensatory mechanisms. CONCLUSION: Compared with the hepatic steatosis of obesity and diabetes, steatosis in ATGL deficiency is well tolerated metabolically. ATGLLKO mice will be useful for studying the pathophysiology of hepatic steatosis.