Handbook of experimental pharmacology
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Handb Exp Pharmacol · Jan 2014
ReviewClinical and ethical implications of placebo effects: enhancing patients' benefits from pain treatment.
Expectancy and learning are the core psychological mechanisms of placebo analgesia. They interact with further psychological processes such as emotions and motivations (e.g., anxiety, desire for relief), somatic focus, or cognitions (e.g., attitudes toward the treatment). The development of placebo responsiveness and the actual placebo response in a person is the result of the complex interaction between factors traced back to the individual learning history related to analgesic drugs or treatments and factors of the current context referring to the analgesic or placebo treatment. ⋯ It joins aspects of the learning history (preexisting experiences and preexisting expectations) of a patient with aspects of the current context (current expectation as a result of external and internal situation in which a pain medication/treatment/placebo is taken, e.g., current information about pain medication, current specific context/cues, desire for pain relief, certainty about upcoming pain relief, current expectation about pain reducing course, current selective attention, increased pain experience, or decreased pain experience). In order to exploit placebo efficacy for an analgesic treatment it is worthwhile to assess in which direction each of these factors exerts its influence in order to maximize placebo effects for a specific patient. By applying placebo mechanisms in this differentiated way, the efficacy of pain treatment can be deliberately boosted.
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Handb Exp Pharmacol · Jan 2014
ReviewGreat expectations: the placebo effect in Parkinson's disease.
Our understanding of the neural mechanisms underlying the placebo effect has increased exponentially in parallel with the advances in brain imaging. This is of particular importance in the field of Parkinson's disease, where clinicians have described placebo effects in their patients for decades. ⋯ Neuroimaging studies have demonstrated that placebos stimulate the release of dopamine in the striatum of patients with Parkinson's disease and can alter the activity of dopamine neurons using single-cell recording. When taken together with the findings from other medical conditions discussed elsewhere in this publication, a unified mechanism for the placebo effect in Parkinson's disease is emerging that blends expectation-induced neurochemical changes and disease-specific nigrostriatal dopamine release.
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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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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 2013
ReviewSoluble guanylate cyclase stimulators in pulmonary hypertension.
Soluble guanylate cyclase (sGC) is a key enzyme in the nitric oxide (NO) signalling pathway. On binding of NO to its prosthetic haem group, sGC catalyses the synthesis of the second messenger cyclic guanosine monophosphate (cGMP), which promotes vasodilation and inhibits smooth muscle proliferation, leukocyte recruitment, platelet aggregation and vascular remodelling through a number of downstream mechanisms. The central role of the NO-sGC-cGMP pathway in regulating pulmonary vascular tone is demonstrated by the dysregulation of NO production, sGC activity and cGMP degradation in pulmonary hypertension (PH). ⋯ These promising results suggest that sGC stimulators may constitute a valuable new therapy for PH. Other trials of riociguat are in progress, including a study of the haemodynamic effects and safety of riociguat in patients with PH associated with left ventricular diastolic dysfunction, and long-term extensions of the phase 3 trials investigating the efficacy and safety of riociguat in patients with PAH and chronic thromboembolic PH. Finally, sGC stimulators may also have potential therapeutic applications in other diseases, including heart failure, lung fibrosis, scleroderma and sickle cell disease.