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
ReviewLearned placebo responses in neuroendocrine and immune functions.
The phenomenon of learned placebo responses in neuroendocrine and immune functions is a fascinating example of communication between the brain and both the endocrine and peripheral immune systems. In this chapter, we will give a short overview of afferent and efferent communication pathways, as well as the central mechanisms, which steer the behavioral conditioned immune response. Subsequently, we will focus on data that provides evidence for learned immune responses in experimental animals and learned neuroendocrine and immune placebo responses in humans. ⋯ Together, these findings not only provide an excellent basis to increase our understanding of human biology but may also have far reaching clinical implications. They pave the way for the ultimate aim of employing associative learning protocols as supportive treatment strategies in pharmacological regimens. As a result, medication levels may be reduced, as well as their unwanted side effects, providing a maximized therapeutic outcome to the benefit of the patient.
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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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Recent substantial laboratory and theoretical research hints for different learning mechanisms regulating the formation of placebo and nocebo responses. Moreover, psychological and biological variants may play a role as modulators of learning mechanisms underlying placebo and nocebo responses. In this chapter, we present pioneering and recent human and nonhuman research that has impressively increased our knowledge of learning mechanisms in the context of placebo and nocebo effects across different physiological processes and pathological conditions.