Learned Placebo Responses in Neuroendocrine and Immune Functions

Abstract

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. Finally, we will take a critical look at these learning protocols, to determine whether or not they can be considered a viable additional treatment option to pharmacological regimens in clinical routine. This is fundamental, since there are still a number of issues, which need to be solved, such as the potential reproducibility, predictability, and extinction of the learned neuroendocrine and immune responses. 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.

Placebo effects and their determinants in gastrointestinal disorders

“…Although a full discussion of ethical aspects is beyond the scope of this article (reviewed elsewhere 174,175 ), it is important to draw attention to emerging evidence from clinical trials in patients with IBS, 83 major depression 176 and migraine 171 that 'openlabel' placebo treatment might be efficacious and is also supported by experimental data. 177,178 Similarly, application of conditioning principles could pave the way to reduce the amount of medication needed 179,180 and/or to reduce adverse events such as conditioned nausea. 142,181 These improvements in care could be achieved with the informed consent of patients and thereby overcome ethics restraints in this field.…”

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

“…For example, somatic placebo analgesia can be mediated by cognitive factors such as patients' expectation about a treatment's benefit, as well as by associative learning processes (Colloca et al, 2008;Tracey, 2010a;Colloca, 2014), whereas visceral placebo analgesia seems less responsive to conditioning. In contrast, neuroendocrine or immune function appears to be affected primarily by conditioning and not by patient expectation (Wendt et al, 2014b). We also need to discover when placebo and nocebo responses occur and to analyze the specific situational circumstances and patient characteristics that are particularly amenable to placebo or nocebo responses (Kaptchuk et al, 2008b).…”

“…Similarly, thorough knowledge of the basic mechanisms steering the behavioral conditioning of pharmacological responses will be essential, not just to better understand the brain mechanisms involved in these learning processes but especially to achieve the longterm goal of learned pharmacological responses: to employ these learning paradigms in clinical situations as supportive therapy together with standard pharmacological regimen, the aim being to maximize the therapeutic outcome (Doering and Rief, 2012;Wendt et al, 2014b). Finally, another fascinating scientific question is why did placebo responses develop during evolution (Kaptchuk, 2002(Kaptchuk, , 2011?…”

The Placebo Phenomenon: A Narrow Focus on Psychological Models

“…Unconscious conditioning process, such as placebo effects related to immune or endocrine system responses to perceived stress and pharmacological conditioning, have also been reported in the literature (Albring et al. 2014; Colloca and Miller 2011b; Colloca, Enck, and DeGrazia 2016; Wendt, Albring, and Schedlowski 2014). Although these concepts require further investigation, it is argued that implicit learning of complex contextual information can be acquired in an incidental manner without a person’s full awareness and still induce implicit expectancies that boost placebo and nocebo effects (Rose, Haider, and Büchel 2005).…”