From acute to chronic pain: tapentadol in the progressive stages of this disease entity

OBJECTIVE: Chronic pain is now recognized as a neural disease, which results from a maladaptive functional and structural transformation process occurring over time. In its chronic phase, pain is not just a symptom but also a disease entity. Therefore, pain must be properly addressed, as many patients still report unsatisfactory pain control despite on-going treatment. The selection of the therapy - taking into account the pathophysiological mechanisms of pain - and the right timing can result in a successful analgesic outcome. This review will present the functional and structural modifications leading to chronification of pain, focusing on the role of tapentadol in this setting. MATERIALS AND METHODS: For inclusion in this review, research studies were retrieved via a keyword-based query of multiple databases (MEDLINE, Embase, Cochrane). The search was last updated in November 2016; no limitations were applied. RESULTS: Functional and structural abnormalities of the nervous system associated with pain chronification have been reported in several conditions, including osteoarthritis, chronic back pain, chronic pelvic pain and fibromyalgia. Correct identification and treatment of pain in recurrent/progressive stage is crucial to prevent chronification and related changes in neural structures. Among analgesic drugs, tapentadol, with its dual mechanism of action (opioid agonist and noradrenaline reuptake blocker), has recently resulted active in pain control at both central and spinal level. CONCLUSIONS: Tapentadol represents a suitable candidate for patients at early progressive stage of pain who have developed neuroplasticity with modification of pain pathways. The availability of different doses of tapentadol may help clinicians to tailor treatment based on the individual need of each patient, with the aim to enhance therapeutic appropriateness in the treatment of musculoskeletal and neuropathic pain

TAP reactor investigation of methane coupling over samarium oxide catalysts

The adsorption and reaction characteristics of a Ba/Sr/Sm2O3 catalyst for methane coupling has been investigated using the TAP (Temporal Analysis of Products) reactor system. Pulsed adsorption experiments using methane, oxygen and krypton at temperatures ranging from 17°C to 800°C show that the transient response of methane is similar to that of Kr and is either not adsorbed, or weakly adsorbed on the catalyst. By contrast, oxygen is strongly adsorbed at temperatures above 500°C which suggests incorporation into the lattice with possible formation of surface anions. Pump-probe experiments in which methane and oxygen are introduced over the catalyst were also performed to investigate the effect of lifetimes of suspected surface intermediates on the relative yields of ethane and ethene. It is shown that the relative yields of both species increase with increasing values of the pulse valve time delay between introduction of the oxygen and methane. An explanation of these results using current knowledge and reasonable speculation of the mechanism is provided

Appropriate use of tapentadol: focus on the optimal tapering strategy

Objective: Due to its opioid and non-opioid mechanism of action, tapentadol is considered an atypical opioid with improved gastrointestinal tolerability versus traditional opioids. As for all opioid analgesics it is important to understand how to discontinue a treatment when it is not needed anymore. The aim of this article was to provide an overview of opioid therapy in non-cancer pain, with a specific focus on tapering of tapentadol in patients with chronic non-cancer pain, and suggestions on how to achieve tapering. Methods: Studies for this narrative review were identified via PubMed using a structured search strategy, focusing on management of chronic non-cancer pain with opioids, and the efficacy, tolerability, and pharmacology of tapentadol prolonged release. Publications were limited to English-language articles published within the last ∼10 years. Results: The review discusses the use and discontinuation of opioids in general, as well clinical data on discontinuation of tapentadol specifically. We provide a flow chart, which can be used by clinicians in the context of their own clinical experience to appropriately taper tapentadol in patients with chronic non-cancer pain. The flow chart can be easily tailored to individual patient characteristics, duration of tapentadol treatment, response to progressive dosage reduction, and likelihood of withdrawal symptom occurrence. Conclusions: While tapentadol is associated with a low frequency of opioid withdrawal symptoms after abrupt discontinuation, use of a tapering strategy is prudent. Tapering strategies developed for opioids in general can potentially be safely individualized in tapentadol-treated patients, although research on tapering strategies for tapentadol is required

Pharmacotherapy for Neuropathic Pain: A Review

Neuropathic pain, comprising a range of heterogeneous conditions, is often severe and difficult to manage, and this may result in a chronic condition that negatively affects the overall functioning and quality of life in patients. The pharmacotherapy of neuropathic pain is challenging and for many patients effective treatment is lacking; therefore, evidence-based recommendations are essential. Currently, there is general agreement on which drugs are appropriate for the first-line treatment of neuropathic pain, whereas debate continues regarding second- and third-line treatments. First-line drugs for neuropathic pain include antidepressants (tricyclic antidepressants and serotonin-noradrenaline reuptake inhibitors) and anticonvulsants acting at calcium channels (pregabalin and gabapentin). Second- and third-line drugs for neuropathic pain include topical lidocaine and opioids. Although efficacious in the treatment of neuropathic pain, opioids are not considered to be a first choice because of adverse drug reactions and, more recently, because of concerns about abuse, diversion, and addiction. A clear understanding of the mechanism of action of currently available drugs is an essential step towards an effective clinical approach that aims to tailor therapies both to the specific neuropathic disease and to the needs of an individual patient. This review provides an overview of current drugs available for the treatment of neuropathic pain with an emphasis on their mechanism of action

Synergic combination of the sol-gel method with dip coating for plasmonic devices

Biosensing technologies based on plasmonic nanostructures have recently attracted significant attention due to their small dimensions, low-cost and high sensitivity but are often limited in terms of affinity, selectivity and stability. Consequently, several methods have been employed to functionalize plasmonic surfaces used for detection in order to increase their stability. Herein, a plasmonic surface was modified through a controlled, silica platform, which enables the improvement of the plasmonic-based sensor functionality. The key processing parameters that allow for the fine-tuning of the silica layer thickness on the plasmonic structure were studied. Control of the silica coating thickness was achieved through a combined approach involving sol-gel and dip-coating techniques. The silica films were characterized using spectroscopic ellipsometry, contact angle measurements, atomic force microscopy and dispersive spectroscopy. The effect of the use of silica layers on the optical properties of the plasmonic structures was evaluated. The obtained results show that the silica coating enables surface protection of the plasmonic structures, preserving their stability for an extended time and inducing a suitable reduction of the regeneration time of the chip

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

β-blockers : their new life from hypertension to cancer and migraine

The pharmacological class of \u3b2-blockers includes a plea of molecules with largely different pharmacokinetic and pharmacodynamic characteristics with a protective effect that may span far beyond the cardiovascular system. Although all these compounds share the pharmacological blockade of the adrenergic receptors, each of them is characterized by specific pharmacological properties, including selectivity of action depending on the adrenergic receptors subtypes, intrinsic sympathomimetic activity (ISA), lipid solubility, pharmacokinetic profile, and also other ancillary properties that impact their clinical effect. Their use in the treatment of hypertension has been extensively debated and at the moment a class indication is not present. However, in specific niche of patients, such as in those young individuals in which hypertension is mainly driven by a sympathetic hyperactivation, strong evidence pose \u3b2-Blockers as a highly reasonable \ufb01rst-line treatment. Lipophilic \u3b2-blockers, specifically propranolol and metoprolol, can cross the Blood Brain Barrier and have a Class A indication for the prophylactic treatment of migraine attacks. Moreover, since \u3b2-adrenergic receptors affect the proliferative process of both cancer and immune cells, their blockade has been associated with metastasis reduction in several epithelial and solid organ tumors posing \u3b2-Blockers as a new attractive, inexpensive and relatively safe therapeutic strategy in patients with several types of cancer. However, further dedicated prospective, randomized, placebo-controlled studies are needed to determine the real efficacy of these compounds

Pharmacology of pain

This article discusses the mechanisms of action of the main drugs used to treat pain, in particular inflammatory pain. The drugs are described following a classification based on the steps of pain processing that they primarily affect

Changing the paradigm in postherpetic neuralgia treatment: lidocaine 700 mg medicated plaster

OBJECTIVE: Chronic pain is currently considered a disease state with biopsychosocial consequences and a negative impact on patients' quality of life (QoL). Pain from postherpetic neuralgia (PHN) can persist for months or years and is a prototypical example of chronic pain. We analyzed PHN as a model of chronic pain. including its effects on QoL and clinical aspects. We explored treatment options, focusing on the topical treatment with lidocaine 700 mg medicated plaster (LMP) and how this impacts PHN management.MATERIALS AND METHODS: This article is a narrative review of published studies. Preclinical and clinical studies were retrieved from literature through a search performed in PubMed/MEDLINE.RESULTS: To choose the appropriate treatment for chronic pains, such as PHN, not only efficacy but also tolerability, manageability, practicality, and compliance are important factors. especially in the long term. It is also important to set treatment expectations with the patients as total suppression of pain may be unrealistic. and a balance needs to be found between pain control and the minimization of adverse events. In this respect, LMP may be the best currently available treatment: it is easy to use, has low systemic absorption and thus a low risk for pharmacological interactions. Therefore, treatments can be personalized, and concomitant medications can be added, if needed. Recent data from a real-world study support this view by showing that LMP has superior effectiveness in reducing pain and improving the QoL compared to other commonly used systemic treatments and confirming its good tolerability profile that is mainly characterized by localized skin reactions.CONCLUSIONS: LMP is one of the best currently available treatment options for PHN patients balancing good efficacy with an excellent tolerability profile and can therefore be considered for use as a first-line treatment for PHN

Osteoarticular pain : therapeutic approach by paradigms

Osteoarticular pain is a common condition in the adult population. It is a nociceptive pain modulated by different factors, and it is one of the major symptoms that force patients to seek medical advice. Since osteoarticular pain has a complex pathophysiology and it is not a linear condition, we propose in this paper an original approach to osteoarticular pain by paradigms, where a paradigm refers to a framework of concepts, results, and procedures within which subsequent work is structured. The paradigm presented is a conceptual tool that could help clinicians to choose the correct therapy considering both pain characteristics and clinical features