Current opinion in pharmacology
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Curr Opin Pharmacol · Apr 2012
ReviewDrug-eluting stent implantation for coronary artery disease: current stents and a comparison with bypass surgery.
Percutaneous coronary intervention (PCI) with bare-metal stents (BMS) has been performed increasingly ever since its introduction in the late 1970s. BMS have been replaced by drug-eluting stents (DES), and many interventional cardiologists consider this as a breakthrough therapy that might compete with coronary artery bypass grafting (CABG) as the standard treatment for coronary artery disease. ⋯ This review described what these agents are and provides an overview regarding the outcomes and associated adverse events. More importantly, this review compares outcomes of PCI with DES to CABG for patients with left anterior descending coronary artery involvement, left main involvement, or multivessel disease.
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Epigenetic changes are chemical modifications to chromatin that modulate gene activity without altering the DNA sequence. While research on epigenetics has grown exponentially over the past few years, very few studies have investigated epigenetic mechanisms in relation to pain states. However, epigenetic mechanisms are crucial to memory formation that requires similar synaptic plasticity to pain processing, indicating that they may play a key role in the control of pain states. This article reviews the early evidence suggesting that epigenetic mechanisms are engaged after injury and in chronic pain states, and that drugs used clinically to target the epigenetic machinery for the treatment of cancer might be useful for the management of chronic pain.
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Curr Opin Pharmacol · Feb 2012
ReviewHyperalgesia by synaptic long-term potentiation (LTP): an update.
Long-term potentiation of synaptic strength (LTP) in nociceptive pathways shares principle features with hyperalgesia including induction protocols, pharmacological profile, neuronal and glial cell types involved and means for prevention. LTP at synapses of nociceptive nerve fibres constitutes a contemporary cellular model for pain amplification following trauma, inflammation, nerve injury or withdrawal from opioids. It provides a novel target for pain therapy. This review summarizes recent progress which has been made in unravelling the properties and functions of LTP in the nociceptive system and in identifying means for its prevention and reversal.
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Curr Opin Pharmacol · Feb 2012
ReviewNeurotherapeutics to inhibit exocytosis from sensory neurons for the control of chronic pain.
There is a pressing unmet need for long-acting and effective therapeutics to alleviate symptoms of the varied forms of chronic pain. As many sufferers do not respond satisfactorily to non-addictive anti-nociceptives, a new treatment has emerged using inhibitors for the release of pain mediators from peripheral sensory nerves to give prolonged benefit. This strategy relies on proteolytically inactivating intra-neuronal SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptors) proteins which are essential for regulated exocytosis of transmitters, peptides and other pain signalling molecules. ⋯ Moreover, an engineered chimera of BoNT/E in which its binding domain was replaced with that from /A efficaciously inhibits the TRPV1 (transient receptor potential vanilloid type 1)-triggered release of CGRP (calcitonin gene-related peptide) from cultured sensory neurons, and suppresses the resultant excitatory effects in brain slices. A longer acting composite toxin, containing the protease of type E attached to BoNT/A, displays prolonged amelioration of pain symptoms in an animal model of inflammatory pain. This provides proof of principle that therapeutically advantageous features of /E (most robust inhibitor of CGRP release) and /A (targeting to sensory neurons and dramatic extension of the longevity of E protease) can be incorporated into a single synergistically active anti-nociceptive.