Validation, reproducibility and safety of trans dermal electrical stimulation in chronic pain patients and healthy volunteers

Background: Surrogate pain models have been extensively tested in Normal Human Volunteers (NHV). There are few studies that examined pain models in chronic pain patients. Patients are likely to have altered pain mechanisms. It is of interest to test patient pain responses to selective pain stimuli under controlled laboratory conditions. Methods: The Institutional Ethic Committee approved the study. 16 patients with chronic neuropathic radiculopathy and 16 healthy volunteers were enrolled to the study after obtaining informed consent. During electrical stimulation (150 minutes for volunteers and 75 minutes for patients) the following parameters were measured every 10 minutes: Ongoing pain: Visual Analogue Scale (VAS) and Numeric Rate Scale (NRS) Allodynia (soft foam brush) Hyperalgesia (von Frey monofilament 20 g) Flare For each endpoint, the area under the curve (AUC) was estimated from the start of stimulation to the end of stimulation by the trapezoidal rule. The individual AUC values for both periods were plotted to show the inter- and intra-subject variability. For each endpoint a mixed effect model was fitted with random effect subject and fixed effect visit. The estimate of intra-subject variance and the mean value were then used to estimate the sample size of a crossover study required to have a probability of 0.80 to detect a 25% change in the mean value. Analysis was done using GenStat 8(th) edition. Results: Each endpoint achieved very good reproducibility for patients and NHV. Comparison between groups revealed trends towards: Faster habituation to painful stimuli in patients Bigger areas of hyperalgesia in patients Similar area of allodynia and flare (no statistical significance) Conclusion: The differences demonstrated between patients and NHVs suggest that the electrical stimulation device used here may stimulate pathways that are affected in the pathological state

Enhanced hydrogen production from thermochemical processes

To alleviate the pressing problem of greenhouse gas emissions, the development and deployment of sustainable energy technologies is necessary. One potentially viable approach for replacing fossil fuels is the development of a H2 economy. Not only can H2 be used to produce heat and electricity, it is also utilised in ammonia synthesis and hydrocracking. H2 is traditionally generated from thermochemical processes such as steam reforming of hydrocarbons and the water-gas-shift (WGS) reaction. However, these processes suffer from low H2 yields owing to their reversible nature. Removing H2 with membranes and/or extracting CO2 with solid sorbents in situ can overcome these issues by shifting the component equilibrium towards enhanced H2 production via Le Chatelier's principle. This can potentially result in reduced energy consumption, smaller reactor sizes and, therefore, lower capital costs. In light of this, a significant amount of work has been conducted over the past few decades to refine these processes through the development of novel materials and complex models. Here, we critically review the most recent developments in these studies, identify possible research gaps, and offer recommendations for future research

Protecting aesthetic innovations? An exploration of the use of registered community designs

A decade after their introduction, approximately three-quarters of a million European registered community designs (RCDs) have been filed, and recent court cases suggest firms regard them as important for competition. This paper reviews design protection in the European Union, discusses this legal instrument to protect designs and design innovations, and provides an overview of how RCDs are used by firms from different countries and industries. To develop a more detailed understanding of their usage, we also report an exploratory qualitative study on the use of RCDs by German firms in three industries: footwear, car manufacturing and tool-making. This revealed some important differences, notably between judicious filing and “all-you-can-file” strategies, which implies that future research using this instrument requires attention be paid to firm and industry level behaviors. We develop a set of propositions, and set out a research agenda

Current knowledge of buprenorphine and its unique pharmacological profile

Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other \u3bc-opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full \u3bc-opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain

Spinal endocannabinoids and CB1 receptors mediate C-fiber-induced heterosynaptic pain sensitization

Diminished synaptic inhibition in the spinal dorsal horn is a major contributor to chronic pain. Pathways that reduce synaptic inhibition in inflammatory and neuropathic pain states have been identified, but central hyperalgesia and diminished dorsal horn synaptic inhibition also occur in the absence of inflammation or neuropathy, solely triggered by intense nociceptive (C-fiber) input to the spinal dorsal horn. We found that endocannabinoids, produced upon strong nociceptive stimulation, activated type 1 cannabinoid (CB1) receptors on inhibitory dorsal horn neurons to reduce the synaptic release of gamma-aminobutyric acid and glycine and thus rendered nociceptive neurons excitable by nonpainful stimuli. Our results suggest that spinal endocannabinoids and CB1 receptors on inhibitory dorsal horn interneurons act as mediators of heterosynaptic pain sensitization and play an unexpected role in dorsal horn pain-controlling circuits