Handbook of experimental pharmacology
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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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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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The pseudounipolar sensory neurons of the dorsal root ganglia (DRG) give rise to peripheral branches that convert thermal, mechanical, and chemical stimuli into electrical signals that are transmitted via central branches to the spinal cord. These neurons express unique combinations of tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na(+) channels that contribute to the resting membrane potential, action potential threshold, and regulate neuronal firing frequency. The small-diameter neurons (<25 μm) isolated from the DRG represent the cell bodies of C-fiber nociceptors that express both TTX-S and TTX-R Na(+) currents. ⋯ Post-translational regulation of Na(+) channels by protein kinases (PKA, PKC, MAPK) alter the expression and function of the channels. Injury-induced changes in these signaling pathways have been linked to sensory neuron hyperexcitability and pain. This review examines the signaling pathways and regulatory mechanisms that modulate the voltage-gated Na(+) channels of sensory neurons.
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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
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.