Chronic Cancer-Related Pain: Continuous Perineural Infusion of Local Anesthetics as Alternative to Systemic Analgesic Drugs.

Pain is a major concern for patients suffering from cancer. Although opioid drugs remain the gold standard for treatment of pain, little is known about the interest of continuous analgesia techniques as alternative. The aim of the present article is to detail the feasibility and to present the diversity of continuous perineural infusion of local anesthetic. A series of five patients suffering from different cancer-related pain is presented. A continuous perineural block was proposed to patients presenting with unbearable pain in an area innervated by a plexus or a nerve despite parenteral analgesic pharmacotherapy. All blocks were performed in a surgical theatre under sterile conditions. An initial bolus dose with 3.75 mg/mL ropivacaine was injected followed by a continuous infusion of 2 mg/mL of ropivacaine. Patient-controlled perineural analgesia was started at home by a nursing network. The technique, the efficacy, and the side effects were reported. Complete pain relief was noted 15 minutes after local anesthetic injection in the five cases, and efficacy was maintained during the following days at home, with no other analgesic treatment required. One patient restarted working a few weeks after catheter insertion. The catheter duration lasted for 12 to 110 days. One catheter was removed because of local anesthetic leak at the puncture point. Some paresthesia was noted in one patient. No other side effect was noted. No infection was reported. In selected patients, continuous perineural infusion of local anesthetics appears to be an attractive alternative to parenteral opioids for cancer-related pain. Further investigation is warranted to better define the place of these techniques in the armamentarium of cancer-related pain treatment.

Guinea pig phospholipase B, identification of the catalytic serine and the proregion involved in its processing and enzymatic activity.

Guinea pig phospholipase B (GPPLB) is a glycosylated ectoenzyme of intestinal brush border membrane. It displays a broad substrate specificity and is activated by trypsin cleavage. The primary sequence contains four tandem repeat domains (I to IV) and several serines in lipase consensus sequences. We used site-directed mutagenesis to demonstrate that only the serine 399 present in repeat II is responsible for the various enzymatic activities of GPPLB. Furthermore, we characterized for the first time the retinyl esterase activity of the enzyme. We also constructed and expressed in COS-7 cells, an NH(2)-terminal repeat I deletion mutant which was detected at a very low level by immunoblot. However, confocal microscopy study showed a strong intracellular accumulation with a weak membrane expression of the mutated protein, indicating a role of the NH(2)-terminal repeat I in the processing of GPPLB. Nevertheless, the Western blot-detected protein presented a glycosylation and trypsin sensitivity patterns similar to wild type PLB. The mutant is also fully active without trypsin treatment, in contrast to native enzyme. Thus, we propose a structural model for GPPLB, in which the repeat I constitutes a lid covering the active site and impairing enzymatic activity, its removal by trypsin leading to an active protein.