Elisa Grella

The antinociceptive effect of tramadol in the formalin test is mediated by the serotonergic component

The aim of this study was to investigate the neurotransmissions involved in the antinociceptive effect of tramadol in the formalin test, which is an animal model of acute and tonic pain. A subcutaneous injection of formalin produces a biphasic nociceptive response: phase 1 (0-10 min-acute pain) and phase 2 (21-60 min-tonic pain). Nociceptive activity is reduced greatly during the 10 min between these two phases. We measured in mice the effects of (+/-)-tramadol, and of (+)- and (-)-tramadol administered before the induction of pain by formalin, in the presence and absence of drugs that act on the opioidergic, serotonergic and noradrenergic systems (naloxone, ketanserin, fluoxetine, maprotiline). With respect to animals treated with formalin alone, (+/-)-tramadol and its enantiomers significantly reduced the duration of nociceptive behaviours (lifting, licking, favouring, shaking, and flinching of the formalin-treated paw) during phase 2. This effect was prevented by the 5-HT(2) receptor antagonist ketanserin, but not by naloxone which, on the contrary, was able to prevent the antinociceptive effect of morphine. Naloxone and ketanserin did not affect the duration of nociceptive behaviour in animals not treated with tramadol. Fluoxetine (a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor), but not maprotiline (a selective norepinephrine reuptake inhibitor), potentiated the antinociceptive effect of (+/-)-tramadol. In conclusion, we demonstrate that the serotonergic pathway is responsible for the antinociceptive effect of tramadol in phase 2 of the formalin test, and that this effect is mediated by 5-HT(2) receptors.

Buprenorphine in long-term control of chronic pain in cancer patients.

The aim of this randomized open-label prospective study was to evaluate the analgesic activity of buprenorphine in a transdermal formulation for cancer chronic pain control versus sustained-release morphine, in all cases combined with oral tramadol. A transdermal system with 35 microg/h buprenorphine was applied to the first group of patients (BT); the second group received 60 mg/day of sustained-release morphine (MT). In both groups oral tramadol was administered to a maximum of 200 mg daily, in case of need. The administration of transdermal buprenorphine versus morphine resulted in significant differences in the physical pain (P = 0.01), mental health (P = 0.03) and vitality (P = 0.001). These data indicated that the BT group showed an improvement of pain and a positive effect on the quality life.

Changing the Metabolic Profile by Large-Volume Liposuction: A Clinical Study Conducted with 123 Obese Women

Adipose tissue is a metabolically active tissue. The hypertrophic fat cells of obese patients produce increased quantities of leptin and tumor necrosis factor-α (TNF-α) and are less sensitive to insulin. This study aimed to determine whether aspirating large amounts of these subcutaneous fat cells by large-volume liposuction (LVL), could change the metabolic profile in 123 obese women. All the patients had a main central body fat distribution (waist–hip ratio, 0.91±0.01) and a body mass index of 32.8 ± 0.8 kg/m). They were studied for 90 days after LVL to determine their changes in insulin sensitivity, resting metabolic rate, serum adipocytokines, and inflammatory marker levels. During 3 months of follow-up evaluation, LVL resulted in a significantly improved insulin sensitivity, resting metabolic rate, serum adipocytokines, and inflammatory marker levels. Such parameters correlate with a decrease in fat mass and waist–hip ratio. Interestingly, no significant changes were seen between the first (21 days) and second (90 days) metabolic determinations after LVL. However, these findings, confirm other preliminary data published previously, and could change the actual role of LVL in the multidisciplinary treatment of obesity.

Modification of Cysteinyl Leukotriene Receptor Expression in Capsular Contracture: Preliminary Results

The development of a fibrotic capsule around foreign material in the body is a physiologic reaction undertaken by the body to protect itself from a material it does not recognize. The periprosthetic capsule can pathologically contract, pressing on the implant; it can cause pain, firmness, and sometimes implant extrusion. The pathogenesis of capsular contracture is still unclear, but most reports indicate a multifactorial explanation. The aim of this study is to investigate the role of cysteinyl leukotriene receptors (cysLTR) on the inflammatory cells involved in the development of the capsular contracture. We recruited 20 patients affected by severe capsular contracture (Baker III–IV) and a control group composed of normal patients who had undergone implant substitution. In both groups, we performed a semiquantitative analysis of mRNA encoding for cysLTR1, cysLTR2, tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10) on myofibroblasts and macrophages of the periprosthetic capsular tissue. The molecular analysis showed an increase in the cysLTR2, TNF-α gene expression but no change in the cysLTR1 and IL-10 genes in patients affected by capsular contracture. These preliminary findings suggest a primary role for cysteinyl leukotrienes in the activation and up-regulation of capsular contraction mechanisms.

Opioids Switching with Transdermal Systems in Chronic Cancer Pain

BackgroundDue to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapyObjectiveTo assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment.MethodsA total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeksResultsPain relief as assessed by VAS, PPI, and PRI significantly improved (p < 0.0001) in all patients at all 3 follow up visits. After 3 weeks of treatment, the reduction in the mean VAS, PPI, and PRI scores in the fentanyl and buprenorphine groups was 68, 77, 74, and 69, 79, and 62%, respectively. Over the same time period the use of oral morphine as rescue medication was reduced from 27.5 ± 20.5 (mean ± SD) to 3.75 ± 8.06, and 33.8 ± 18.9 to 3.75 ± 10.9 mg/day in the fentanyl and buprenorphine groups, respectively. There was no significant difference in either pain relief or rescue medication use between the two patient groups The number of patient with adverse events fell during the study. After the third week of the treatment the number of patients with constipation was reduced from 11 to 5, and 10 to 4 patients in the fentanyl and buprenorphine groups, respectively. There was a similar reduction in the incidence of nausea and vomiting. No sedation was seen in any patient after one week of treatment.ConclusionOpioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

Modification of Cysteinyl Leukotriene Receptors Expression in Capsular Contracture: Follow-up Study and Definitive Results

Periprosthetic capsular contracture represents a specific iatrogenic phenomenon with different side effects. Recently, interesting data have disclosed a potential role of leukotrienes as important mediators of inflammation in the reactivation process of capsular contracture. Some preliminary studies have assessed the efficacy of leukotriene antagonists in the prevention and treatment of capsular contracture. These clinical data are still lacking of a potential biomolecular basis. The aim of our present study was to evaluate the expression of the protein receptor cysteinyl leukotriene receptors (CysLTR). We included 50 patients with severe capsular contracture (Baker III–IV) and a control group consisting of healthy patients who underwent an implant replacement. In both groups, we performed the protein extraction and semiquantitative analysis for the determination of protein concentration on myofibroblasts and macrophages. Western Blot analysis of protein levels shows a significant increase in the expression of CysLTR in patients with capsular contracture. Our final results show that the increase in the levels of mRNA coding for CysLTR actually translates into an effective increase in protein levels of these mRNA transcripts. These findings could at least partially provide a biomolecular basis that justifies the use of specific antileukotriene drugs in the treatment of this disease.

Hepatic omphalocele in an adult

The finding of an untreated omphalocele in adulthood is extremely rare. We report the case of a 29‐year‐old patient, who presented to us with a congenital defect of the abdominal wall and protrusion of underlying viscera.

Histologic Analysis of Zafirlukast's Effect on Capsule Formation Around Silicone Implants: some considerations.

We have read with profound interest the article by Bastos and colleagues entitled Histologic Analysis of Zafirlukast’s Effect on Capsule Formation Around Silicone Implants. We have truly enjoyed this study because it focuses on the very important issue of ongoing research toward pharmacologic therapy for the treatment of periprosthetic capsule contracture. The latter has an incidence in the range of 0.5% to 50% [3]. Despite persistent clinical and laboratory investigation, to date, no solution has been developed to solve or prevent this problem. For several years, many investigators have evaluated the use of antileukotriene drugs, which could be effective in the treatment of periprosthetic capsule contracture. Unfortunately, their use still is not evidence based and has no biochemical or biomolecular support. At the same time, the use of drugs with no specific indication is strongly criticized and discouraged for moral, medical, and legal reasons [6]. Investigations into a molecular basis to justify the use of CysLT antagonists have evaluated the potential modification of cysLTR expression in human contracted capsules [2]. The conclusions of the study by Bastos and colleagues are supported by several clinical studies, which are reviewed in their studies. However, the authors failed to review the animal models proposed to date (rabbits, pigs, rats). Although these animal studies are very accurate, they have disadvantages in terms of reproducibility, standardization, and of course translation to the human setting [1, 4, 5, 7]. In all the experiments, the authors tried to induce contracture through different methods (bacterial contamination, fibrin glue), stressing the fundamental cellular and biochemical difference between the contracted capsule and the physiologic periprosthetic capsule. Unfortunately, Bastos and colleagues used an animal model that, in our opinion, is not accurate with respect to a contracted capsule. Indeed, the authors did not induce capsular contracture in their animal model. With the fundamental differences between contracted and uncontracted capsules in mind, the immunohistochemical and histopathology analysis was carried out on periprosthetic physiologic capsules. Thus, the reduced presence of inflammatory cells and the reduced vascular density in the experimental groups (explained by the intrinsic antiinflammatory activity of zafirlukast) cannot definitely be proof of a therapeutic effect of the drug in reducing or preventing capsular contracture. Moreover, it is unclear why the authors decided to remove the prostheses 90 days after the implantation to analyze the capsules, assuming them to be contracted. Despite these criticisms, we thank Bastos and colleagues for focusing their attention on a very serious problem in plastic surgery and for proposing a histologic and immunohistochemical analysis of the development of capsular contraction. We hope that many other investigators will undertake the same approach in fighting against this frustrating problem that afflicts patients, plastic surgeons, and manufacturers.

643 EFFICACY OF TRAMADOL AS LOCAL ANAESTHETIC IN RECONSTRUCTIVE PLASTIC SURGERY

641 PRELIMINARY STUDY OF COGNITIVE AND EMOTIONAL PREDICTORS OF POST-SURGERY PAIN IN PATIENTS SUBMITTED TO GYNECOLOGIC AND ORTHOPEDIC SURGERY P. Pinto *, A. Almeida, C. Correia, T. McIntyre. School of Psychology, Minho University, Braga, Portugal; School of Health Sciences, Minho University, Braga, Portugal; Alto Ave Hospital Center, Guimarães, Portugal; Department of Psychology, University of Houston, Houston, United States