Current pharmaceutical design
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Editorial Comment
Coping with neuropathic pain: do we need more selective analgesic drugs?
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Spinal cord injuries (SCI) result in a devastating loss of function below the level of the lesion in which there are variable motor recoveries and, in the majority of cases, central neuropathic pain syndromes (CNP) develop several months to years following injury. Unfortunately, the study of chronic pain after SCI has been neglected in the past due in part to the lack of good animal models but largely due to the clinically held dogma that CNP is not a real phenomenon and is psychogenic in nature rather than based on described pathophysiological mechanisms. The purpose of this article is to offer standardized terminology of pain, insight into animal modeling issues of CNP, descriptions of current clinical therapies and to discuss the pathophysiological mechanisms that provide the substrate for CNP that will lead to innovative new therapies. It is hoped that this information will give insight for research strategies as well as better care not only of SCI individuals, but is generalizable to many other CNP syndromes.
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Early postpartum hemorrhage remains a significant cause of maternal morbidity and mortality. Postpartum hemorrhage is most commonly due to uterine atony and often responds to medical treatments such as administration of uterotonic drugs, alone or in combination with uterine massage or bimanual compression. As the incidence of cesarean section continues to rise, the problem of placenta previa and accreta is likely to become more common. ⋯ In recent years new therapeutic measures to control the bleeding have gained attention. Although, these newer therapies focus on avoiding the need for emergency hysterectomy and preservation of reproductive function, reports of subsequent pregnancies are still scarce. Established management options are shortly reviewed and novel medical and surgical treatments are more extensively discussed.
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Opiates lack potent analgesic efficacy in neuropathic pain although it is now generally accepted that the poor effect of these drugs reflects a reduction in their potency. Reduction of morphine antinociceptive potency was postulated to be due to the fact that nerve injury altered the activity of opioid systems or opioid specific signaling. ⋯ Opioid peptides biosynthesis and opioid receptors density in the nociceptive pathways and their functions change under various conditions associated with neuropathic pain following damage to the spinal cord and injury of peripheral nerves. Identification of a role of opioid systems in neuropathic pain and molecular and cellular mechanisms underlying these processes are of importance to understanding of the opioid action in neuropathic pain that will hopefully facilitate development of therapeutic strategies in which effectiveness of opioids in alleviation neuropathic pain is increased.
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In most mammals purine degradation ultimately leads to the formation of allantoin. Humans lack the enzyme uricase, which catalyzes the conversion of uric acid to allantoin. The resulting higher level of uric acid has been hypothesized to play a role as an antioxidant. ⋯ The mechanisms by which MSU crystals lead to an acute inflammatory arthritis are under investigation and current knowledge is reviewed here. Treatment of gout includes management of acute flares with anti-inflammatory medications such as non-steroidal anti-inflammatory drugs or corticosteroids and long term management with urate-lowering therapy when indicated. Future directions in the treatment of gout, in part guided by a better understanding of pathophysiology, are discussed.