Handbook of experimental pharmacology
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Handb Exp Pharmacol · Jan 2014
ReviewAnimal toxins influence voltage-gated sodium channel function.
Voltage-gated sodium (Nav) channels are essential contributors to neuronal excitability, making them the most commonly targeted ion channel family by toxins found in animal venoms. These molecules can be used to probe the functional aspects of Nav channels on a molecular level and to explore their physiological role in normal and diseased tissues. This chapter summarizes our existing knowledge of the mechanisms by which animal toxins influence Nav channels as well as their potential application in designing therapeutic drugs.
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Placebo analgesia has become a well-studied phenomenon that encompasses psychology, physiology and pharmacology. In this chapter we explore the complex interactions between these disciplines in order to argue that the placebo response is more than a simple change in perception but is a cognitive style driven by prior expectations. ⋯ This altered sensation can be attributed to personality traits, altered error monitoring processes, changes in anticipatory responses to pain and activation of the endogenous opioid system. In conclusion we discuss how altered sensory processing by descending pain modulation may play a part in placebo analgesia and how the loss of the brains prefrontal regions can make it impossible to have a placebo response.
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Handb Exp Pharmacol · Jan 2014
Lessons to be learned from placebo arms in psychopharmacology trials.
Large placebo effects are typically reported in clinical drug trials and evidence suggests placebo effects have increased over time. The diminishing drug-placebo difference calls into question the effectiveness of pharmacological treatments and provides a challenge to prove the effectiveness of new medications. This chapter discusses explanations for the increasing placebo effect. ⋯ It is argued that specific and nonspecific effects interact in drug groups of clinical trials. This interaction influences drug-placebo differences in clinical trials (i.e., trial sensitivity). Future research should aim to identify which patients will respond best to drugs and those who may be better treated with placebos.
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Physical complaints, such as pain, can be effectively altered by placebo and nocebo effects due to induction of positive or negative expectations. While verbal suggestion and conditioning are recognized as playing a key role in placebo and nocebo effects on pain, these mechanisms have barely been investigated with regard to other somatosensory sensations, such as itch. Results on contagious itch in both animals and humans suggest that itch sensations might be even more susceptible for placebo and nocebo effects than pain. ⋯ Recent work also demonstrated that placebo and nocebo effects on itch sensations were most effectively induced by procedures that consist of both conditioning and verbal suggestion principles. This work adds to previous prospective studies showing that expectation mechanisms, such as preservative worrying about negative consequences, are relatively consistent predictors of future disease outcomes, including itch, in chronic somatic conditions. Future studies should focus on the specific psychoneurobiological mechanisms of placebo and nocebo effects in various physical sensations, to get insight into the common and specific effects and to contribute to the long-term and clinically relevant use of placebo effects in clinical practice.
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Handb Exp Pharmacol · Jan 2014
ReviewTraditional and innovative experimental and clinical trial designs and their advantages and pitfalls.
Many study designs and design variants have been developed in the past to either overcome or enhance drug-placebo differences in clinical trials or to identify and characterize placebo responders in experimental studies. They share many commonalities as well as differences that are discussed here: the role of deception and ethical restrictions, habituation effects and the control of the natural course of disease, assay sensitivity testing and effective blinding, acceptability and motivation of patients and volunteers, and the development of individualized medicine. These are fostered by two opposite strategies: utilizing the beneficial aspects of the placebo response-and avoiding its negative counterpart, the nocebo effect-in medical routine for the benefit of patients, and minimizing-by controlling-the negative aspects of the placebo effect during drug development.