Frontiers in pharmacology
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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
Inhibition of voltage-gated sodium channels by sumatriptan bioisosteres.
Voltage-gated sodium channels are known to play a pivotal role in perception and transmission of pain sensations. Gain-of-function mutations in the genes encoding the peripheral neuronal sodium channels, hNav1.7-1.9, cause human painful diseases. Thus while treatment of chronic pain remains an unmet clinical need, sodium channel blockers are considered as promising druggable targets. ⋯ Accordingly, we show that (S)-22b likely binds the conserved local anesthetic receptor within voltage-gated sodium channels. Combining these results with the previous ones, we hypothesize that use-dependent sodium channel blockade contributes to the analgesic activity of (R)-31b and (S)-22b. These later compounds represent promising lead compounds for the development of efficient analgesics, the mechanism of action of which may include a dual action on sodium channels and 5HT1D receptors.
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Frontiers in pharmacology · Jan 2015
ReviewA Review of Swertia chirayita (Gentianaceae) as a Traditional Medicinal Plant.
Swertia chirayita (Gentianaceae), a popular medicinal herb indigenous to the temperate Himalayas is used in traditional medicine to treat numerous ailments such as liver disorders, malaria, and diabetes and are reported to have a wide spectrum of pharmacological properties. Its medicinal usage is well-documented in Indian pharmaceutical codex, the British, and the American pharmacopeias and in different traditional medicine such as the Ayurveda, Unani, Siddha, and other conventional medical systems. This ethnomedicinal herb is known mostly for its bitter taste caused by the presence of different bioactive compounds that are directly associated with human health welfare. ⋯ In this regard, plant biotechnological applications such as micropropagation, synthetic seed production, and hairy root technology can play a significant role in a holistic conservation strategy. In addition to micropropagation, storage of these valuable genetic resources is equally important for germplasm preservation. However, more advanced research is warranted to determine the activities of bioactive compounds in vitro and in vivo, establish their underlying mechanisms of action and commence the process of clinical research.
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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.