The effect of systemic lidocaine on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers

Although effective in neuropathic pain, the efficacy of systemic lidocaine in non-neuropathic pain remains uncertain. We investigated the analgesic effect of systemic lidocaine on the heat/capsaicin sensitization model of experimental pain in 24 volunteers. Sensitization was produced by heating the skin to 45 degrees C for 5 min, followed by a 30-min application of 0.075% capsaicin cream, and maintained by periodically reheating the sensitized skin. Subjects received IV lidocaine (bolus 2 mg/kg, then infusion 3 mg. kg. h), or saline for 85 min. Areas of secondary hyperalgesia, heat pain detection thresholds, and painfulness of stimulation with 45 degrees C for 1 min (long thermal stimulation) were quantified. Systemic lidocaine reduced the area of secondary hyperalgesia to brush, but not to von Frey hair stimulation. Lidocaine did not alter heat pain detection thresholds or painfulness of long thermal stimulation in normal skin. We conclude that, at infusion rates in the low- to mid-antiarrhythmic range, lidocaine has no effect on acute nociceptive pain but does have a limited and selective effect on secondary hyperalgesia. Implications: The efficacy of systemic lidocaine in nonneuropathic pain remains uncertain. This study investigates the effect of systemic lidocaine on experimental-induced hyperalgesia in 25 volunteers. Hyperalgesia was induced by using an experimental pain model that uses heat and capsaicin in combination. Systemic lidocaine showed a selective effect on secondary hyperalgesia.     

Quantitative assessment of intravascular volume of the human Achilles tendon

The pathogenesis of Achilles tendon rupture remains unclear, but vascular patterns may play an important role. We determined the intravascular volume of the Achilles tendon using a new method with injection of radioisotopes. A solution of Tc-99m and gelatin-ink was injected into the lower limbs of body donors. The intravascular volume of each 1 cm section of the Achilles tendon was measured using a gamma well counter. We found that the distal part of the Achilles tendon (0-2 cm above the calcaneus) had an intravascular volume of 59-98 microL/g tendon tissue. In the middle part of the tendon (3-6 cm above the calcaneal insertion), the intravascular volume was much less: 2743 microL/g tissue. The proximal part of the tendon (7-9 cm) had an intravascular volume between 51-100 microL/g tendon tissue. The reduced vascularization in the middle part of the human Achilles tendon may play a role in degeneration and spontaneous rupture of the tendon.     

Genotyping of presenilin-1 polymorphism in amyotrophic lateral sclerosis

The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n=72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P < 0.04) and allele (P < 0.03) distribution between patients and controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis. Received: 14 February 2000 / Received in revised form: 20 April 2000 / Accepted: 4 June 2000     

Tenascin-X,collagen, and Ehlers–Danlos syndrome: Tenascin-X gene defects can protect against adverse cardiovascular events

Long thought to be two separate syndromes, Ehlers–Danlos syndrome hypermobility type (EDS-HT) and benign joint hypermobility syndrome (BJHS) appear on close examination to represent the same syndrome, with virtually identical clinical manifestations. While both EDS-HT and BJHS were long thought to lack the genetic loci of other connective tissue disorders, including all other types of EDS, researchers have discovered a genetic locus that accounts for manifestations of both EDS-HT and BJHS in a small population of patients. However, given the modest sample size of these studies and the strong correlation between serum levels of tenascin-X with clinical symptoms of both EDS-HT and BJHS, strong evidence exists for the origins of both types of hypermobility originating in haploinsufficiency or deficiency of the gene TNXB, responsible for tenascin-X.     

Experimental models and therapeutic approaches for HBV

Liver disease associated to persistent infection with the hepatitis B virus (HBV) continues to be a major health problem of global impact. In spite of the existence of an effective vaccine, approximately 360 million people are chronically infected worldwide, who are at high risk of developing liver cirrhosis and hepatocellular carcinoma. Although current therapeutic regimens can efficiently suppress viral replication, the unique replication strategies employed by HBV permit the virus to persist within the infected hepatocytes. As a consequence, relapse of viral activity is commonly observed after cessation of treatment with polymerase inhibitors. The narrow host range of HBV has hindered progresses in understanding specific steps of HBV replication and the development of more effective therapeutic strategies aiming at achieving sustained viral control and, eventually, virus eradication. This review will focus on summarizing recent advances obtained with well-established and more innovative experimental models, giving emphasis on the strength of the different systems as tools for elucidating distinct aspects of HBV persistence and for the development of new therapeutic approaches.