F1000Research
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The search for a "pain centre" in the brain has long eluded neuroscientists. Although many regions of the brain have been shown to respond to painful stimuli, all of these regions also respond to other types of salient stimuli. In a recent paper, Segerdahl et al. (Nature Neuroscience, 2015) claims that the dorsal posterior insula (dpIns) is a pain-specific region based on the observation that the magnitude of regional cerebral blood flow (rCBF) fluctuations in the dpIns correlated with the magnitude of evoked pain. However, such a conclusion is, simply, not justified by the experimental evidence provided. Here we discuss three major factors that seriously question this claim.
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This paper will focus on problems in the inability to double-blind cognitive-behavioral therapy (CBT) studies for major depressive disorder (MDD), and provides an analysis of a recently published study to show how this problem can lead to faulty conclusions. A study by Hollon et al. published in JAMA Psychiatry that compared an antidepressant medication-only arm with a combined CBT/antidepressant arm concluded that the cognitive therapy/antidepressant combination enhanced the recovery rates compared with antidepressant alone, and that the magnitude of this increment nearly doubled for patients with more severe depression. ⋯ We opine that the conclusions of unblind CBT outcome research in conditions with subjective endpoints such as MDD need to be given with great caution. The validity of CBT (and its derivatives such as dialectical behavioral therapy) for indications other than MDD is also part of a larger problem in the inability to blind outcome studies for these interventions.
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Transversus abdominal plane (TAP) block has a long history and there is currently extensive clinical experience around TAP blocks. The aim of this review is to provide a summary of the present evidence on the effects of TAP block and to provide suggestions for further studies. There are several approaches to performing abdominal wall blocks, with the rapid implementation of ultrasound-guided technique facilitating a major difference in TAP block performance. ⋯ TAP block seems an interesting alternative in patients with, for example, severe obesity where epidural or spinal anaesthesia/analgesia is technically difficult and/or poses a risk. There is an obvious need for further high-quality studies comparing TAP block prior to surgery with local infiltration analgesia, single-shot spinal analgesia, and epidural analgesia. These studies should be procedure-specific and the effects should be evaluated, both regarding short-term pain and analgesic requirement and also including the effects on postoperative nausea and vomiting, recovery of bowel function, ambulation, discharge, and protracted recovery outcomes (assessed by e.g., postoperative quality of recovery scale).
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Several programmed lytic and necrotic-like cell death mechanisms have now been uncovered, including the recently described receptor interacting protein kinase-3 (RIPK3)-mixed lineage kinase domain-like (MLKL)-dependent necroptosis pathway. Genetic experiments have shown that programmed necrosis, including necroptosis, can play a pivotal role in regulating host-resistance against microbial infections. ⋯ We discuss the critical function of phosphorylation in the execution of necroptosis, and highlight the emerging regulatory roles for several ubiquitin ligases and deubiquitinating enzymes. Finally, based on current evidence, we discuss the potential mechanisms by which the essential, and possibly terminal, necroptotic effector, MLKL, triggers the disruption of cellular membranes to cause cell lysis.
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Sevoflurane has been available for clinical practice for about 20 years. Nowadays, its pharmacodynamic and pharmacokinetic properties together with its absence of major adverse side effects on the different organ systems have made this drug accepted worldwide as a safe and reliable anesthetic agent for clinical practice in various settings.