Handbook of experimental pharmacology
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Handb Exp Pharmacol · Jan 2014
Meta AnalysisA meta-analysis of brain mechanisms of placebo analgesia: consistent findings and unanswered questions.
Placebo treatments reliably reduce pain in the clinic and in the lab. Because pain is a subjective experience, it has been difficult to determine whether placebo analgesia is clinically relevant. Neuroimaging studies of placebo analgesia provide objective evidence of placebo-induced changes in brain processing and allow researchers to isolate the mechanisms underlying placebo-based pain reduction. ⋯ Other brain regions showed reliable increases in activation with expectations for reduced pain. These included the prefrontal cortex (including dorsolateral, ventromedial, and orbitofrontal cortices), the midbrain surrounding the periaqueductal gray, and the rostral anterior cingulate. We discuss implications of these findings as well as how future studies can expand our understanding of the precise functional contributions of the brain systems identified here.
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Handb Exp Pharmacol · Jan 2014
ReviewPlacebo effects in idiopathic and neuropathic pain conditions.
The magnitude of placebo analgesia effect appears to be large in chronic pain patients experiencing hyperalgesic states. So far, placebo effects have primarily been investigated in idiopathic pain conditions, such as irritable bowel pain syndrome, but more recently they have also been investigated in neuropathic pain patients, in which the underlying nerve injury is known. Expected pain levels and emotional feelings are central to placebo effects in both types of pain. ⋯ Furthermore, expectations, emotional feelings, and the experience of pain seem to interact over time, thereby maintaining or enhancing the pain-relieving effect. Expectations and emotional feelings also contribute to the effect of active drugs, and recent studies indicate that drug effects and placebo effects interact in ways that may complicate the interpretations of the findings from clinical trials. It is suggested that expectations and emotional feelings may act as additional or alternative measures in the testing of new pharmacological agents, thereby improving the understanding of the interaction between pharmacological effects and placebo effects, which may have far-reaching implications for research and clinical practice.
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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.