Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7–10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain.

Background: Placebo and nocebo effects occur in clinical or laboratory medical contexts after administration of an inert treatment or as part of active treatments and are due to psychobiological mechanisms such as expectancies of the patient. Placebo and nocebo studies have evolved from predominantly methodological research into a far-reaching interdisciplinary field that is unravelling the neurobiological, behavioural and clinical underpinnings of these phenomena in a broad variety of medical conditions. As a consequence, there is an increasing demand from health professionals to develop expert recommendations about evidence-based and ethical use of placebo and nocebo effects for clinical practice. Methods: A survey and interdisciplinary expert meeting by invitation was organized as part of the 1st Society for Interdisciplinary Placebo Studies (SIPS) conference in 2017. Twenty-nine internationally recognized placebo researchers participated. Results: There was consensus that maximizing placebo effects and minimizing nocebo effects should lead to better treatment outcomes with fewer side effects. Experts particularly agreed on the importance of informing patients about placebo and nocebo effects and training health professionals in patient-clinician communication to maximize placebo and minimize nocebo effects. Conclusions: The current paper forms a first step towards developing evidence-based and ethical recommendations about the implications of placebo and nocebo research for medical practice, based on the current state of evidence and the consensus of experts. Future research might focus on how to implement these recommendations, including how to optimize conditions for educating patients about placebo and nocebo effects and providing training for the implementation in clinical practice.

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Although it has long been known that psychosocial factors play a crucial role in placebo responses, no attempt has been made to understand if social observation shapes the placebo analgesic effect. To address this question, we compared placebo analgesia induced through social observation (Group 1) with first-hand experience via a typical conditioning procedure (Group 2) and verbal suggestion alone (Group 3). In Group 1, subjects underwent painful stimuli and placebo treatment after they had observed a demonstrator (actually a simulator) showing analgesic effect when the painful stimuli were paired to a green light. In Group 2, subjects were conditioned according to previous studies, whereby a green light was associated to the surreptitious reduction of stimulus intensity, so as to make them believe that the treatment worked. In Group 3, subjects received painful stimuli and were verbally instructed to expect a benefit from a green light. Pain perception was assessed by means of a Numerical Rating Scale (NRS) ranging from 0=no pain to 10=maximum imaginable pain. Empathy trait and heart rate were also measured. We found that observing the beneficial effects in the demonstrator induced substantial placebo analgesic responses, which were positively correlated with empathy scores. Moreover, observational social learning produced placebo responses that were similar to those induced by directly experiencing the benefit through the conditioning procedure, whereas verbal suggestions alone produced significantly smaller effects. These findings show that placebo analgesia is finely tuned by social observation and suggest that different forms of learning take part in the placebo phenomenon.

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