Handbook of experimental pharmacology
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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
ReviewThe pharmacology of voltage-gated sodium channels in sensory neurones.
Voltage-gated sodium channels (VGSCs) are vital for the normal functioning of most excitable cells. At least nine distinct functional subtypes of VGSCs are recognized, corresponding to nine genes for their pore-forming alpha-subunits. These have different developmental expression patterns, different tissue distributions in the adult and are differentially regulated at the cellular level by receptor-coupled cell signalling systems. ⋯ We discuss in detail how drugs and toxins interact with archetypal VGSCs and where possible consider how they act on VGSCs in peripheral sensory neurones. Increasingly, drugs that block VGSCs are being used as systemic analgesic agents in chronic pain syndromes, but the full potential for VGSC blockers in this indication is yet to be realized and other applications in sensory dysfunction are also possible. Drugs targeting VGSC subtypes in sensory neurones are likely to provide novel systemic analgesics that are tissue-specific and perhaps even disease-specific, providing much-needed novel therapeutic approaches for the relief of chronic pain.
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Handb Exp Pharmacol · Jan 2009
ReviewClinical cough II: therapeutic treatments and management of chronic cough.
Chronic cough is a common and frequently disruptive symptom which can be difficult to treat with currently available medicines. Asthma/eosinophilic airway disease and gastro-oesophageal reflux disease are most commonly associated with chronic cough but it may also trouble patients with chronic obstructive pulmonary disease, pulmonary fibrosis and lung cancer. Over the last three decades there have been a number of key advances in the clinical approach to cough and a number of international guidelines on the management of cough have been developed. ⋯ The main objective of new treatments for cough would be to identify ways to downregulate this heightened cough reflex but yet preserve its crucial role in protecting the airway. The combined efforts of clinicians, scientists and the pharmaceutical industry offer most hope for such a treatment breakthrough. The aim of this chapter is to provide some rationale for the current treatment recommendations and to offer some reflections on the management of patients with chronic cough.
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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
ReviewCough sensors. I. Physiological and pharmacological properties of the afferent nerves regulating cough.
The afferent nerves regulating cough have been reasonably well defined. The selective effects of general anesthesia on C-fiber-dependent cough and the opposing effects of C-fiber subtypes in cough have led to some uncertainty about their regulation of this defensive reflex. But a role for C-fibers in cough seems almost certain, given the unique pharmacological properties of these unmyelinated vagal afferent nerves and the ability of many C-fiber-selective stimulants to evoke cough. ⋯ These "cough receptors" are distinct from the slowly and rapidly adapting intrapulmonary stretch receptors responding to lung inflation. Indeed, intrapulmonary rapidly and slowly adapting receptors and pulmonary C-fibers may play no role or a nonessential role in cough, or might even actively inhibit cough upon activation. A critical review of the studies of the afferent nerve subtypes most often implicated in cough is provided.