Handbook of experimental pharmacology
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Handb Exp Pharmacol · Jan 2014
ReviewHow positive and negative expectations shape the experience of visceral pain.
Knowledge from placebo and nocebo research aimed at elucidating the role of treatment expectations and learning experiences in shaping the response to visceral pain fills an important research gap. First, chronic abdominal pain, such as in irritable bowel syndrome (IBS), is highly prevalent, with detrimental individual and socioeconomic impact and limited effective treatment options. At the same time, IBS patients show high placebo response rates in clinical trials and benefit from placebo interventions. ⋯ Hence, the study of nocebo and placebo effects in visceral pain constitutes a model to assess the contribution of psychological factors. Herein, the clinical relevance of visceral pain is introduced with a focus on IBS as a bio-psycho-social disorder, followed by a review of existing clinical and experimental work on placebo and nocebo effects in IBS and in clinically relevant visceral pain models. Finally, emerging research trends are highlighted along with an outlook regarding goals for ongoing and future research.
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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
ReviewProbing gating mechanisms of sodium channels using pore blockers.
Several classes of small molecules and peptides bind at the central pore of voltage-gated sodium channels either from the extracellular or intracellular side of the membrane and block ion conduction through the pore. Biophysical studies that shed light on the chemical nature, accessibility, and kinetics of binding of these naturally occurring and synthetic compounds reveal a wealth of information about how these channels gate. Here, we discuss insights into the structural underpinnings of gating of the channel pore and its coupling to the voltage sensors obtained from pore blockers including site 1 neurotoxins and local anesthetics.
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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.