There is a growing interest in the enhancement of human potential by means of non-invasive brain neuromodulatory techniques. Transcranial direct current stimulation (tDCS) is a type of neuromodulatory technique that shows great promise as it is low cost, safe, well tolerated, clinically applicable and capable of inducing long term behavioral after-effects. Placebo and nocebo effects are a critical component of clinical care and efficacy studies. Harnessing these effects by directly modulating the excitability of certain brain regions will have a significantly high impact on both medical practice and neuroscience. The goal of this proposal is to explore how excitability changes in the right dorsolateral prefrontal cortex (rDLPFC) induced by tDCS can modulate placebo analgesia and nocebo hyperalgesia in both healthy and patient populations. In Experiment 1, we will use a well-tested expectancy manipulation model to compare the subjective pain ratings and fMRI signal changes evoked by an inert lidocaine (placebo), capsaicin (nocebo), and neutral control cream in three groups of healthy subjects. In Group 1, tDCS will be used to enhance the excitability of the rDLPFC; in Group 2, tDCS will be used to inhibit the excitability of the rDLPFC and in Group 3, sham tDCS will be applied. In Experiment 2, we will extend the study to chronic low back pain (cLBP) patients. First, we will boost patients' expectations of the analgesic effect through a combination of placebo lidocaine cream and sham tDCS using the expectancy modulation model. Then we will investigate if enhancing the excitability of rDLPFC by repeated tDCS can be used to enhance the analgesia associated with the placebo cream treatment of experimental heat pain. Furthermore, we will explore if the boosted expectancy can also enhance the placebo effect of lidocaine cream treatment on endogenous low back pain (a clinical outcome). The ability to enhance and inhibit excitability of specific brain regions in humans and investigate its effect on human behavior is key to understanding brain function and circuitry. Using devices such as tDCS allows us to move forward from observation to a more mechanistic understanding of neural causation. The results achieved in this study will shed new light on harnessing the self-control capacities to optimize the placebo and nocebo effects in clinical practice and research, facilitating development of new pain management methods and elucidating the relationship between the human brain and behavior.
Placebo and nocebo responses have significant clinical implications. The aim of this study is to use transcranial direct current stimulation (tDCS), a non invasive, safe, inexpensive, and clinically applicable brain stimulation tool, to modulate (enhance or inhibit) placebo and nocebo effects in healthy and patient populations. We believe that our findings will facilitate the development of methods to harness placebo and nocebo effects in a clinical setting.
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