Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2015
ReviewOpioid-induced hyperalgesia in chronic pain patients and the mitigating effects of gabapentin.
Chronic pain patients receiving opioid drugs are at risk for opioid-induced hyperalgesia (OIH), wherein opioid pain medication leads to a paradoxical pain state. OIH involves central sensitization of primary and secondary afferent neurons in the dorsal horn and dorsal root ganglion, similar to neuropathic pain. ⋯ However, few human studies investigating gabapentin use in OIH have been performed in recent years. In this review, we discuss the potential mechanisms that underlie OIH and provide a critical overview of interventional therapeutic strategies, especially the clinically-successful drug gabapentin, which may reduce OIH.
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Frontiers in pharmacology · Jan 2015
ReviewPost-translational modifications of voltage-gated sodium channels in chronic pain syndromes.
In the peripheral sensory nervous system the neuronal expression of voltage-gated sodium channels (Navs) is very important for the transmission of nociceptive information since they give rise to the upstroke of the action potential (AP). Navs are composed of nine different isoforms with distinct biophysical properties. Studying the mutations associated with the increase or absence of pain sensitivity in humans, as well as other expression studies, have highlighted Nav1.7, Nav1.8, and Nav1.9 as being the most important contributors to the control of nociceptive neuronal electrogenesis. ⋯ In this review we will discuss the role of Protein Kinase A, B, and C, Mitogen Activated Protein Kinases and Ca++/Calmodulin-dependent Kinase II in peripheral chronic pain syndromes. We will also discuss more recent findings that the ubiquitination of Nav1.7 by Nedd4-2 and the effect of methylglyoxal on Nav1.8 are also implicated in the development of experimental neuropathic pain. We will address the potential roles of other PTMs in chronic pain and highlight the need for further investigation of PTMs of Navs in order to develop new pharmacological tools to alleviate pain.
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Frontiers in pharmacology · Jan 2015
A hemodynamic model to guide blood pressure control during deliberate hypotension with sodium nitroprusside in children.
Sodium nitroprusside (SNP) has been widely used to control blood pressure in infants and children. The goals of this analysis were to develop models that describe the hemodynamic response to SNP dosing in pediatric patients; examine sources of variation in dose-response, defining age, and size dependencies; and determine vulnerable populations or patient subtypes that may elicit dosing modifications. A multi-center, randomized, double-blinded, parallel-group, dose-ranging, effect-controlled study, followed by an open-label dose titration of an intravenous infusion of SNP was undertaken in 203 pediatric subjects, who required deliberate hypotension or controlled normotension during anesthesia. ⋯ The infusion rate producing 50% of Emax (ER50) at steady state for high EC50, was 0.34 μg/kg/min and for low EC50 0.103 μg/kg/min. The K-PD model well-describes initial dosing of SNP under controlled circumstances; model-based dosing guidance agrees with current practice. An initial titration strategy supported via algorithm-based feedback should improve maintenance of target MAP.
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Frontiers in pharmacology · Jan 2015
ReviewNutrition, a health technology that deserves increasing interest among HTA doers. A systematic review.
The increasing interest for evaluating indirect consequences of health care interventions and their interaction with patients' behavior have put the focus on health promotion interventions including nutrition and the need to measure and evaluate them. ⋯ the reports included correspond to HiC while those HTA agencies established in Low and Middle Income countries (LMiC) have no reported or written activities on the role of nutrition and nutrition interventions. Retrieved reports written by HTA doers/producers confirm the use and utility of systematic reviews and economic analysis methods and its applicability for nutrition interventions. However, some measurements such as Quality Adjusted Life Years (QALY) need to be refined to better reflect the impact of these interventions.
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Frontiers in pharmacology · Jan 2015
ReviewThe scale of the evidence base on the health effects of conventional yogurt consumption: findings of a scoping review.
The health effects of conventional yogurt have been investigated for over a century; however, few systematic reviews have been conducted to assess the extent of the health benefits of yogurt. ⋯ This scoping review has revealed the extensive evidence base for many outcomes which could be the focus of systematic reviews exploring the health effects of conventional yogurt consumption.