Although placebos have long been considered a nuisance in clinical research, today they represent an active and productive field of research and, because of the involvement of many mechanisms, the study of the placebo effect can actually be viewed as a melting pot of concepts and ideas for neuroscience. Indeed, there exists not a single but many placebo effects, with different mechanisms and in different systems, medical conditions, and therapeutic interventions. For example, brain mechanisms of expectation, anxiety, and reward are all involved, as well as a variety of learning phenomena, such as Pavlovian conditioning, cognitive, and social learning. There is also some experimental evidence of different genetic variants in placebo responsiveness. The most productive models to better understand the neurobiology of the placebo effect are pain and Parkinson's disease. In these medical conditions, the neural networks that are involved have been identified: that is, the opioidergic-cholecystokinergic-dopaminergic modulatory network in pain and part of the basal ganglia circuitry in Parkinson's disease. Important clinical implications emerge from these recent advances in placebo research. First, as the placebo effect is basically a psychosocial context effect, these data indicate that different social stimuli, such as words and rituals of the therapeutic act, may change the chemistry and circuitry of the patient's brain. Second, the mechanisms that are activated by placebos are the same as those activated by drugs, which suggests a cognitive/affective interference with drug action. Third, if prefrontal functioning is impaired, placebo responses are reduced or totally lacking, as occurs in dementia of the Alzheimer's type.

Placebo and nocebo effects are embodied psycho-neurobiological responses capable of modulating pain and producing changes at different neurobiological, body at perceptual and cognitive levels. These modifications are triggered by different contextual factors (CFs) presented in the therapeutic encounter between patient and healthcare providers, such as healing rituals and signs. The CFs directly impact on the quality of the therapeutic outcome: a positive context, that is a context characterized by the presence of positive CFs, can reduce pain by producing placebo effects, while a negative context, characterized by the presence of negative CFs, can aggravate pain by creating nocebo effects. Despite the increasing interest about this topic; the detailed study of CFs as triggers of placebo and nocebo effects is still lacked in the management of musculoskeletal pain.Increasing evidence suggest a relevant role of CFs in musculoskeletal pain management. CFs are a complex sets of internal, external or relational elements encompassing: patient’s expectation, history, baseline characteristics; clinician’s behavior, belief, verbal suggestions and therapeutic touch; positive therapeutic encounter, patient-centered approach and social learning; overt therapy, posology of intervention, modality of treatment administration; marketing features of treatment and health care setting. Different explanatory models such as classical conditioning and expectancy can explain how CFs trigger placebo and nocebo effects. CFs act through specific neural networks and neurotransmitters that were described as mediators of placebo and nocebo effects.Available findings suggest a relevant clinical role and impact of CFs. They should be integrated in the clinical reasoning to increase the number of treatment solutions, boosts their efficacy and improve the quality of the decision-making. From a clinical perspective, the mindful manipulation of CFs represents a useful opportunity to enrich a well-established therapy in therapeutic setting within the ethical border. From a translational perspective, there is a strong need of research studies on CFs close to routine and real-world clinical practice in order to underline the uncertainty of therapy action and help clinicians to implement knowledge in daily practice.

Placebos have been shown to induce powerful effects in a variety of medical conditions, such as pain and movement disorders, as well as to increase physical performance and endurance in healthy subjects. Here we investigated the effects of an ergogenic placebo on the performance of the quadriceps muscle, which is responsible for the extension of the leg relative to the thigh. In a first experiment, a placebo was administered along with the suggestion that it was caffeine at high dose. This resulted in a significant increase in mean muscle work across subjects, which, however, was not accompanied by a decrease of perceived muscle fatigue. In a second experiment, the placebo caffeine was administered twice in two different sessions. Each time, the weight to be lifted with the quadriceps was reduced surreptitiously so as to make the subjects believe that the 'ergogenic agent' was effective. After this conditioning procedure, the load was restored to the original weight, and both muscle work and perceived fatigue assessed after placebo administration. Compared with the first experiment, the placebo effect was larger, with a significant increase in muscle work and decrease in perceived muscle fatigue. Within the context of the role of peripheral and/or central mechanisms in muscle performance, the present findings suggest a central mechanism of top-down modulation of muscle fatigue. In addition, the difference between the first and second experiment underscores the role of learning in increasing muscle performance with placebos.

No abstract

Pain is a sensory and emotional experience that is substantially modulated by psychological, social and contextual factors. Research now indicates that the influence of these factors is even more powerful than expected and involves the therapeutic response to analgesic drugs as well as the pain experience itself, which in some circumstances can even be a form of reward. Different experimental approaches and models, both in the laboratory and in the clinical setting, have been used to better characterize and understand the complex neurobiology of pain modulation. These approaches include placebo analgesia, nocebo hyperalgesia, hidden administration of analgesics, and the manipulation of the pain-reward relationship. Overall, these studies show that different neurochemical systems are activated in different positive and negative contexts. Moreover, pain can activate reward mechanisms when experienced within contexts that have special positive meaning. Because routine medical practice usually takes place in contexts that use different rituals, these neurobiological insights might have profound clinical implications.

Background: Placebo and nocebo effects embody psychoneurobiological phenomena where behavioural, neurophysiological, perceptive and cognitive changes occur during the therapeutic encounter in the healthcare context. Placebo effects are produced by a positive healthcare context; while nocebo effects are consequences of negative healthcare context. Historically, placebo, nocebo and context-related effects were considered as confounding elements for clinicians and researchers. In the last two decades this attitude started to change, and the understanding of the value of these effects has increased. Despite the growing interest, the knowledge and the awareness of using the healthcare context to trigger placebo and nocebo effects is currently limited and heterogeneous among physiotherapists, reducing their translational value in the physiotherapy field. Objectives: To introduce the placebo, nocebo and context-related effects by: (1) presenting their psychological models; (2) describing their neurophysiological mechanisms; (3) underlining their impact for the physiotherapy profession; and (4) tracing lines for future researches. Conclusion: Several psychological mechanisms are involved in placebo, nocebo and context-related effects; including expectation, learning processes (classical conditioning and observational learning), reinforced expectations, mindset and personality traits. The neurophysiological mechanisms mainly include the endogenous opioid, the endocannabinoid and the dopaminergic systems. Neuroimaging studies have identified different brain regions involved such as the dorsolateral prefrontal cortex, the rostral anterior cingulate cortex, the periaqueductal gray and the dorsal horn of spine. From a clinical perspective, the manipulation of the healthcare context with the best evidence-based therapy represents an opportunity to trigger placebo effects and to avoid nocebo effects respecting the ethical code of conduct. From a managerial perspective, stakeholders, organizations and governments should encourage the assessment of the healthcare context aimed to improve the quality of physiotherapy services. From an educational perspective, placebo and nocebo effects are professional topics that should be integrated in the university program of health and medical professions. From a research perspective, the control of placebo, nocebo and context-related effects offers to the scientific community the chance to better measure the impact of physiotherapy on different outcomes and in different conditions through primary studies.

No abstract

Although the great increase in interest in the placebo phenomenon was spurred by the clinical implications of its use, the progressive elucidation of the neurobiological and pharmacological mechanisms underlying the placebo effect also helps cast new light on the relationship between mind (and brain) and body, a topic of foremost philosophical importance but also a major medical issue in light of the complex interactions between the brain on the one hand and body functions on the other. While the concept of placebo can be a general one, with a broad definition generally applicable to many different contexts, the description of the cerebral processes called into action in specific situations can vary widely. In this paper, examples will be given where physiological or pathological conditions are altered following the administration of an inert substance or verbal instructions tailored to induce expectation of a change, and explanations will be offered with details on neurotransmitter changes and neural pathways activated. As an instance of how placebo effects can extend beyond the clinical setting, data in the physical performance domain and implications for sport competitions will also be presented and discussed.