Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials

Chronic pain is a major source of morbidity for which there are limited effective treatments. Palmitoylethanolamide (PEA), a naturally occurring fatty acid amide, has demonstrated utility in the treatment of neuropathic and inflammatory pain. Emerging reports have supported a possible role for its use in the treatment of chronic pain, although this remains controversial. We undertook a systematic review and meta-analysis to examine the efficacy of PEA as an analgesic agent for chronic pain. A systematic literature search was performed, using the databases MEDLINE and Web of Science, to identify double-blind randomized controlled trials comparing PEA to placebo or active comparators in the treatment of chronic pain. All articles were independently screened by two reviewers. The primary outcome was pain intensity scores, for which a meta-analysis was undertaken using a random effects statistical model. Secondary outcomes including quality of life, functional status, and side effects are represented in a narrative synthesis. Our literature search identified 253 unique articles, of which 11 were ultimately included in the narrative synthesis and meta-analysis. Collectively, these articles described a combined sample size of 774 patients. PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standard mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001). Several studies reported additional benefits of PEA for quality of life and functional status, and no major side effects were attributed to PEA in any study. The results of this systematic review and meta-analysis suggest that PEA is an effective and well-tolerated treatment for chronic pain. Further study is warranted to determine the optimal dosing and administration parameters of PEA for analgesic effects in the context of chronic pain

Hyperbare Oxygenierung in der Schmerztherapie : eine mechanismenbasierte Darstellung und eine Bewertung der Wirksamkeit bei ausgewählten Schmerzbildern

Akute und chronische Schmerzen stellen in der Medizin eine große Herausforderung dar, und nicht zuletzt aufgrund der demographischen Entwicklung ist von einer steten Zunahme der Patientenzahlen mit akuten und chronischen Schmerzen auszugehen. Die Pathophysiologie wird in den letzten Jahren zunehmend besser verstanden, wodurch rationale Begründungen für neue Therapieformen Platz finden. Neben anderen physikalischen Therapiemaßnahmen hat die Hyperbare Oxygenierung Einzug in die Schmerztherapie gehalten. Hyperbare Oxygenierung (HBO) ist eine Therapieform, bei welcher Patienten in speziellen Druckkammern 100% Sauerstoff unter erhöhtem Umgebungsdruck atmen. In tierexperimentellen Untersuchungen konnten in Assoziation zu HBO-Therapie eine Reihe von molekularbiologischen und biochemischen Mechanismen festgestellt werden, welche möglicherweise Einfluss auf die Schmerzentstehung und Schmerzverarbeitung Einfluss haben. Ziel dieser Arbeit soll sein, einen Überblick über tierexperimentelle Studien zu bieten, welcher wiederum die Grundlage für das Verständnis und die Interpretation der zu Verfügung stehenden Humandaten bildet. In den Datenbanken PubMed und Ovid Medline wurde eine systematische Literatursuche durchgeführt. Dadurch konnten 35 Studien mit insgesamt 612 Patienten herausgefiltert werden. Eine Auswertung erfolgte unter zwei Gesichtspunkten: Zum einen wurden die vor allem in Tierstudien gezeigten zugrundeliegenden Mechanismen exzerpiert, und zum anderen wurde die klinische Anwendbarkeit anhand von Humanstudien evaluiert. Insgesamt konnte gezeigt werden, dass die HBO durchaus, sowohl alternativ als auch additiv, als effektive Methode in der Behandlung chronischer Schmerzen zu sehen ist. Unklar ist sicherlich noch das optimale Dosis-Wirkungsverhältnis. Sowohl um optimale Behandlungsprotokolle, als auch um die Evidenz zu stärken, sind weitere ausreichend gepowerte, hochwertige Untersuchungen v.a. mit Humandaten notwendig.Introduction/Background: As a consequence of several traumata and risk factors patients can develop an acute respiratory distress syndrome (ARDS). It is defined as an acute lung injury (developing in a time span of less than a week) with pulmonary infiltrations on both sides, not being explained by other causes such as embolism or cardiac decompensation, with a Horovitz ratio (PaO2/FiO2) below 300. In the process of developing ARDS several immune processes involving different immune cells, which until now have not been specified, play an important role. Aim/Objectives: The study aims to quantify the regional, alveolar specific immune response of patients with ARDS. This will help depict the involved immune processes more accurately. Materials and Methods: In order to gain cells for the consecutive flow cytometry analysis, peripheral blood is taken from the patients, together with bronchoalveolar lavage (BAL). BAL is a procedure to clarify immunologic or infectious processes going within the alveolar compartment. For BAL a bronchoscopy is performed, during which 0.9% saline solution is instilled and aspirated in order to gain airway cells, immune cells or bacteria. The blood and the BAL fluid are consequentially analyzed at the laboratory of the clinical department for hematology by fluorescence flow cytometry in order to quantify the different immune cells according to their specific CD surface markers. Summary/Conclusion: Flow cytometry of BAL provides a mean to monitor the immunologic processes within the alveolar compartment and allows for quantifying the temporal and qualitative processes of the immune response to ARDS.vorgelegt von: Kordula Lang-IllievichMedizinische Universität Wien, Masterarb., 2017Medizinische Universität Wien, Diplomarbeit, 201

Ketamine as Treatment for Cluster Headache: A Systematic Review of Literature and a Case Series

Abstract Introduction Cluster headache is a severe and debilitating neurological condition characterized by intense, excruciating pain with a significant impact on patients' wellbeing. Although different treatment options are available, many patients continue to experience inadequate relief. Therefore, experimental strategies are increasingly studied. One of the more promising approaches is the use of ketamine. We present the currently available evidence and our own data. Methods In this mixed-methods paper, we first summarize the available evidence of ketamine for treatment of cluster headache based on a systematic review of literature in MEDLINE, EMBASE and the Cochrane library of systematic reviews. As the level of evidence is quite limited, we report our own cohort study with ten patients treated with ketamine infusions for cluster headache. They were followed up to investigate the patients’ experience of treatment success and quality of life. Results The search and review of literature identified four reports with a total of 68 patients. All were uncontrolled case series. The current literature suggests that ketamine might decrease cluster headache. However, as the applied regimes and reported outcomes are highly heterogeneous, further analysis was futile. Our own data show high patient satisfaction with ketamine treatment. Conclusion Despite the limited evidence, ketamine might be considered a potential therapeutic approach for cluster headache. Therefore, further research including randomized controlled trials should be encouraged

The Effect of Palmitoylethanolamide on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers—A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial

Palmitoylethanolamide (PEA) is marketed as a “dietary food for special medical purposes”. Its broad-spectrum analgesic, anti-inflammatory, and neuroprotective effects make PEA an interesting substance in pain management. However, the underlying analgetic mechanisms have not yet been investigated in humans. The aim of our study is to provide a deeper understanding of the involved mechanisms, which is essential for differentiating therapeutic approaches and the establishment of mechanism-based therapeutic approaches. In this randomized, placebo-controlled, double-blinded crossover trial, 14 healthy volunteers were included. PEA (3 × 400 mg per day) or placebo were taken for 4 weeks. Our study investigated the mode of action of PEA using an established pain model, “Repetitive phasic heat application”, which is well-suited to investigate analgesic and anti-hyperalgesic effects in healthy volunteers. Parameters for peripheral and central sensitization as well as for pain modulation were assessed. Repetitive heat pain was significantly decreased, and the cold pain tolerance was significantly prolonged after the PEA treatment. The pressure pain tolerance and the conditioned pain modulation were increased after the PEA treatment. The wind-up ratio and the average distance of allodynia were significantly decreased after the PEA treatment. The heat pain tolerance was significantly higher after the PEA treatment. The present study has demonstrated that PEA has clinically relevant analgesic properties, acting on both peripheral and central mechanisms as well as in pain modulation

The effect of photobiomodulation on histamine and Mucuna pruriens-induced pruritus, hyperknesis and alloknesis in healthy volunteers: A double-blind, randomized, sham-controlled study.

BackgroundPhotobiomodulation, also referred to as Low-Level Light Therapy (LLLT), has emerged as a promising intervention for pruritus, a prevalent and often distressing symptom.ObjectivesThis study investigated the efficacy of low-level light therapy (LLLT) in alleviating pruritus, hyperknesis, and alloknesis induced by histamine and Mucuna pruriens.MethodsIn a double-blind, randomized, sham-controlled trial with a split-body design, healthy volunteers underwent 6 minutes of LLLT and sham treatments in separate upper back quadrants. The histamine model was applied to the upper quadrants, and Mucuna pruriens to the lower quadrants. Pruritus intensity, alloknesis, hyperknesis, flare area, and skin temperature were measured pre and post treatment.ResultsSeventeen individuals (eight females, nine males) participated in the study. In the histamine model, LLLT notably reduced itch intensity (difference = 13.9 (95% CI: 10.5 - 17.4), p = 0.001), alloknesis (difference = 0.80 (95% CI: 0.58-1.02), p = 0.001), and hyperknesis (difference = 0.48 (95% CI: 0.09-0.86), p = 0.01). Skin temperature changes were not significantly different between the two groups (difference = -2.0 (95% CI: -6.7-2.6), p = 0.37). For the Mucuna pruriens model, no significant differences were observed in any measures, including itch intensity (difference = 0.8 (95% CI: -2.3 - 3.8), p = 0.61) hyperknesis (difference = 0.08 (95% CI: -0.06-0.33), p = 0.16) and alloknesis (difference = 0. 0.09 (95% CI: -0.08-0.256), p = 0.27).ConclusionsLLLT effectively reduced histamine-induced pruritus, alloknesis, and hyperknesis; however, LLLT was ineffective against Mucuna pruriens-induced pruritus. Further investigations are required to determine LLLT's effectiveness of LLLT in various pruritus models