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
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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Simple, rapid and inexpensive rodent models of nicotine physical dependence and withdrawal syndrome have proved useful for preliminary screening of smoking cessation treatments. They have led to an exponential increase of knowledge regarding the underlying neurobiological mechanisms of dependence and withdrawal syndrome. The human nicotine withdrawal syndrome in smoking cessation is variable and multidimensional, involving irritability, anxiety, depression, cognitive and attentional impairments, weight gain, sleep disturbances, and craving for nicotine. ⋯ For example, depression-like phenomena may involve alterations in mechanisms such as the mesolimbic dopamine pathway from the ventral tegmental area to the nucleus accumbens. Irritability and anxiety may involve alterations in endogenous opioid systems and other regions, such as the amygdala. This chapter reviews many additional anatomical, neurochemical, and developmental elements that impact nicotine physical dependence.