Handbook of experimental pharmacology
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Migraine is a neurovascular disorder which affects one fifth of the general population. Disability due to migraine is severe and involves patients from infancy through senescence and it is aggravated by the fact there is no complete cure. ⋯ These novel antagonists block the receptor for the sensory neuropeptide calcitonin gene-related peptide (CGRP), which upon release from peripheral terminals of trigeminal perivascular neurons dilates cranial arterial vessels. Whether neurogenic vasodilatation is the major contributing factor to generate the pain and the associated symptoms of the migraine attack or whether other sites of action of CGRP receptor antagonists are responsible for the antimigraine effect of these compounds is the subject of current and intense research.
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Handb Exp Pharmacol · Jan 2009
ReviewCough sensors. V. Pharmacological modulation of cough sensors.
Several airway afferent nerve subtypes have been implicated in coughing. These include bronchopulmonary C-fibers, rapidly adapting airway mechanoreceptors and touch-sensitive tracheal Adelta-fibers (also called cough receptors). ⋯ In this review we catalogue the chemical agents that stimulate and/or modulate the activity of the airway afferent nerves involved in cough, and describe the specific mechanisms involved in these effects. In addition, we describe the mechanisms of action of a number of chemical inhibitors of these afferent nerve subtypes, and attempt to relate this information to the regulation of coughing in health and disease.
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The prevalence of people suffering from chronic pain is extremely high and pain affects millions of people worldwide. As such, persistent pain represents a major health problem and an unmet clinical need. The reason for the high incidence of chronic pain patients is in a large part due to a paucity of effective pain control. ⋯ However, there is considerable hope for the development of new classes of analgesic drugs by targeting novel processes contributing to clinically relevant pain. In this chapter we highlight a number of molecular species which are potential therapeutic targets for future neuropathic pain treatments. In particular, the roles of voltage-gated ion channels, neuroinflammation, protein kinases and neurotrophins are discussed in relation to the generation of neuropathic pain and how by targeting these molecules it may be possible to provide better pain control than is currently available.
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Handb Exp Pharmacol · Jan 2009
Clinical cough IV:what is the minimal important difference for the Leicester Cough Questionnaire?
The Leicester Cough Questionnaire (LCQ) is a valid, reproducible, responsive self-reported cough-specific health status measure. It has been used to assess overall efficacy of treatments for cough, but its threshold for clinical significance, or patient importance, is unknown. The aim of this study was to determine the minimal important difference (MID) of the LCQ for patients with chronic cough; this is the smallest change in quality-of-life score considered to be clinically meaningful. ⋯ We have demonstrated that the LCQ MID is 1.3. The LCQ MID should aid clinicians and researchers to make meaningful interpretations of health-related quality-of-life data relating to chronic cough.
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Handb Exp Pharmacol · Jan 2009
ReviewSkin aquaporins: function in hydration, wound healing, and skin epidermis homeostasis.
Several aquaporins (AQPs) are expressed in mammalian skin. Some are directly involved in water transport, such as AQP5, which is involved in sweat secretion. In contrast, the physiological role of skin aquaglyceroporins, which permeate both water and glycerol, appears more and more complex. ⋯ Both water and glycerol transport by AQP3 appear to play an important role in hydration of mammalian skin epidermis. In addition, recent data suggest that glycerol transport by AQP3 is involved in the metabolism of lipids in skin as well as in the regulation of proliferation and differentiation of keratinocytes. Finally, AQP3 is also believed to be important in wound healing, as a water channel by facilitating cell migration, and as a glycerol transporter by enhancing keratinocyte proliferation and differentiation.