The Emerging Neurobiology of Placebo and Nocebo

Session Title: The Emerging Neurobiology of Placebo and Nocebo

Topic: BASIC SCIENCE

Description of Workshop: The placebo effect has long been known to be an important element of pain treatment, and its “evil twin”, the nocebo effect, also has a robust effect on the prognosis of chronic pain patients. The opioid mediation of placebo analgesia and cholecystokinin mediation of nocebo hyperalgesia was demonstrated many decades ago, but very little else was known. Recently, however, there has been an explosion of new knowledge about the neuroanatomy and neurophysiology of placebo and nocebo effects. Speakers will present recent research on neurobiological mechanisms underlying placebo and nocebo effects in mice and humans.
Placebo and nocebo effects, although extremely important phenomena, have only recently been subject to systematic neurobiological investigations. Two of the talks will describe newly developed mouse models of placebo and nocebo, both used to define neural circuits mediating the phenomena. The third talk will describe the latest knowledge in placebo imaging and functional connectivity results and those of open-label placebo treatment trials.
Greg Scherrer will present both mouse and human data suggesting a crucial role for a circuit linking the cingulate cortex to the cerebellum via the pons in placebo analgesia. Specifically, anatomical and functional studies revealed that this novel pain-modulation circuit, which involves layer 5 pyramidal tract neurons in the cingulate cortex that project onto pontine nucleus neurons that project to cognitive areas of the cerebellum, encodes and is necessary for expectation-based opioidergic pain reduction.
Loren Martin will present mouse data using two distinct paradigms of nocebo hyperalgesia, one involving classical conditioning and the other social learning. In both cases, anatomical and functional studies revealed the necessity of a neural circuit from the anterior cingulate to the lateral periaqueductal gray releasing cholecystokinin.
Ulrike Bingel will present the latest evidence showing that placebo and nocebo effects on pain involve—at least in part—distinct neural pathways and temporal dynamics. In particular, nocebo effects appear to be more easily induced, stronger, and more persistent than placebo effects, as well as more resistant to extinction. These findings have important clinical implications, underscoring the need to prevent the elicitation of nocebo effects and to mitigate their impact on treatment outcomes.

Speakers