Abstract Buprenorphine was not used widely in clinical practice over many years, mainly due to analgesic potency and clinical safety concerns based on misinterpreted animal data. Contrary to previous ...concerns, however, no analgesic ceiling effect and no antagonism of combined pure μ-opioid receptor agonists is seen within the therapeutic dose range. In recent studies, buprenorphine could be effectively and safely combined with full μ-agonists, and switching between buprenorphine and another opioid provided comparable pain relief based on equianalgesic doses. Moreover, buprenorphine exerts an antihyperalgesic effect, which is due—at least in part—to antagonistic activity at κ-opioid receptors. Buprenorphine pharmacokinetics are not altered by advanced age or renal dysfunction. In addition, the risk of respiratory depression is lower than with other opioids including morphine, hydromorphone, methadone and fentanyl. Unlike morphine and fentanyl, there is no immunosuppressive activity with buprenorphine at therapeutic analgesic doses. Transdermal buprenorphine has significantly improved the clinical use of the drug, providing continuous buprenorphine release for up to 96 h. In clinical trials, patients receiving transdermal buprenorphine experienced significantly greater pain relief, better sleep, and a reduced need for rescue therapy, compared to placebo. Large-scale post-marketing studies have confirmed the effectiveness of transdermal buprenorphine in treating moderate-to-severe cancer and non-cancer pain including neuropathic syndromes. Finally, the comparably low incidence of CNS adverse events and constipation, and the possibility of use in severe renal dysfunction without a need for dose adjustment make buprenorphine well suited for chronic pain management in at-risk patients, such as diabetics, elderly or renally impaired individuals including those requiring haemodialysis.
Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management ...strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation.
Significance
Central sensitisation is an important manifestation involved in many different chronic pain conditions. Central sensitisation can be different to assess and evaluate as the manifestations vary from pain condition to pain condition. Understanding central sensitisation may promote better profiling and diagnosis of pain patients and development of new regimes for mechanism based therapy. Some of the mechanisms underlying central sensitisation can be translated from animals to humans providing new options in development of therapies and profiling drugs under development.
The second world-wide failure exercise is an international activity, organised by Kaddour and Hinton, aiming at a better understanding of the limitations of existing failure criteria to predict ...failure under triaxial stressing. The present work is a response to an invitation to take part and employ Hashin's failure criteria to the 12 test cases defined by the organizers of the second world-wide failure exercise. Methods, based on nonlinear analysis, used to perform the required simulations are explained and the predictions are presented. Observed problems are discussed.
The Second World-Wide Failure Exercise is an international activity, organized by Hinton and Kaddour The background to the Second World-Wide Failure Exercise (WWFE-II). 2012., aiming at a better ...understanding of the limitations of existing failure criteria to predict failure under triaxial stressing. Part A of the exercise was to apply the failure criteria to the 12 test cases defined by the organizers of second world-wide failure exercise to predict strength. The presently reported Part B is to compare the predictions with the before unknown strength measurements, also provided by the organizers of second world-wide failure exercise. Hashin’s Failure criteria for unidirectional fiber composites. J Appl Mech 1980; 47(6): 329–334. model is used in its original form with one exception which is explained in the article. Problems with inhomogeneous stress distributions, arising in certain samples, are addressed. The deviations between predictions and measurements are quantified and explanations for those are given for the individual load cases.
This work addresses the problem of finding a substitute material model for describing the load response of globally flat corrugated sheets made from multidirectional laminates. Exact solutions of the ...equations governing thin singly curved shells give the displacements, strains and stresses within a unit cell extending over one period of the corrugation pattern. The forces reacting to enforced unit deformations determine the constitutive law of the substitute material model. The analytical results are compared with those of finite-element models.
Abstract Axonal action potentials initiate the cycle of synaptic communication that is key to our understanding of nervous system functioning. The field has accumulated vast knowledge of the ...signature action potential waveform, firing patterns, and underlying channel properties of many cell types, but in most cases this information comes from somatic intracellular/whole-cell recordings, which necessarily measure a mixture of the currents compartmentalized in the soma, dendrites, and axon. Because the axon in many neuron types appears to be the site of lowest threshold for action potential initiation, the channel constellation in the axon is of particular interest. However, the axon is more experimentally inaccessible than the soma or dendrites. Recent studies have developed and applied single-fiber extracellular recording, direct intracellular recording, and optical recording techniques from axons toward understanding the behavior of the axonal action potential. We are starting to understand better how specific channels and other cellular properties shape action potential threshold, waveform, and timing: key elements contributing to downstream transmitter release. From this increased scrutiny emerges a theme of axons with more computational power than in traditional conceptualizations.
Corrugated laminates have highly anisotropic stiffness properties. Therefore, they are interesting candidates for flexible skins. The geometrically non-linear stiffness response of corrugated sheets ...is crucial for applications with large deformations. The present paper analyzes the governing mechanisms that drive the non-linear tensile behavior and suggests a model to analyze corrugated structures. The mechanical response mainly depends on the geometry such as amplitude and thickness of the corrugation and the material properties. The proposed model calculates the mechanical response based on a simplified model consisting of rods and discrete torsional springs. It is verified by comparison with non-linear structural analysis with FEM and experimentally validated by using samples manufactured by 3D printing. The paper also presents a parametric study investigating the influence of the geometry on the non-linear behavior and we identify the limits of linear approximation of the structural response of corrugated laminates.
Neuropathic pain (NP) is an enormous burden for patients, caregivers and society. NP is a pain state that may develop after injury of the peripheral or central nervous system because of a wide range ...of diseases and traumas. A NP symptom component can be found also in several types of chronic pain. Many NP patients are substantially disabled for years. Due to its chronicity, severity and unpredictability, NP is difficult to treat. Tapentadol is a central-acting oral analgesic with combined opioid and noradrenergic properties, which make it potentially suitable for a wide range of pain conditions, particularly whenever a NP component is present or cannot be excluded. In randomized controlled trials, tapentadol has proved to be effective in relieving NP in diabetic peripheral neuropathy and in chronic low back pain. In observational studies, tapentadol reduced NP in chemotherapy-induced peripheral neuropathies, blood and solid cancers, and the NP component in neck pain and Parkinson's disease. This narrative review aims to provide clinicians with a broad overview of tapentadol effects on NP.
The ideal hypnotic agent for electroconvulsive therapy (ECT) is still under debate and previous studies comparing etomidate and methohexital have produced conflicting results. This retrospective ...study compares etomidate and methohexital as anesthetic agents in continuation and maintenance (m)ECT with regard to seizure quality and anesthetic outcomes.
All subjects undergoing mECT at our department between October 1st, 2014 and February 28th, 2022 were included in this retrospective analysis. Data for each ECT session were obtained from the electronic health records. Anesthesia was performed with either methohexital/succinylcholine or etomidate/succinylcholine. Standard seizure quality parameters, anesthesiological monitoring data, pharmacological interventions and side-effects were recorded.
573 mECT treatments in 88 patients were included (methohexital n = 458, etomidate n = 115). Seizures lasted significantly longer after using etomidate (electroencephalography: +12.80 s 95 %-CI:8.64–16.95; electromyogram +6.59 s 95 %-CI:4.14–9.04). Time to maximum coherence was significantly longer with etomidate (+7.34 s 95 %-CI:3.97–10.71. Use of etomidate was associated with longer procedure duration (+6.51 min 95 %-CI:4.84–8.17) and higher maximum postictal systolic blood pressure (+13.64 mmHg 95 %-CI:9.33–17.94). Postictal systolic blood pressure > 180 mmHg, the use of antihypertensives, benzodiazepines and clonidine (for postictal agitation), as well as the occurrence of myoclonus was significantly more common under etomidate.
Due to longer procedure duration and an unfavorable side effect profile, etomidate appears inferior to methohexital as an anesthetic agent in mECT despite longer seizure durations.
•Hypnotic agents for electroconvulsive therapy must provide high controllability.•Records of 573 maintenance ECT sessions comparing ethomidate and methohexital anesthesia were analyzed.•Seizure and procedure duration was longer when using etomidate.•Use of etomidate was associated with higher postictal systolic blood pressure and other adverse events.•Etomidate appears inferior to methohexital as an anesthetic agent for electroconvulsive therapy.
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