Behavioral/Systems/Cognitive Dissociable Influences of Opiates and Expectations on Pain

Placebo treatments and opiate drugs are thought to have common effects on the opioid systemandpain-related brain processes. This has created excitement about the potential for expectations to modulate drug effects themselves. If drug effects differ as a function of belief, this would challenge the assumptions underlying the standard clinical trial. We conducted two studies to directly examine the relation-ship between expectations and opioid analgesia.We administered the opioid agonist remifentanil to human subjects during experimen-tal thermal pain and manipulated participants ’ knowledge of drug delivery using an open-hidden design. This allowed us to test drug effects, expectancy (knowledge) effects, and their interactions on pain reports and pain-related responses in the brain. Remifentanil and expectancy both reduced pain, but drug effects on pain reports and fMRI activity did not interact with expectancy. Regions associated with pain processing showed drug-induced modulation during both Open and Hidden conditions, with no differences in drug effects as a function of expectation. Instead, expectancymodulated activity in frontal cortex, with a separable time course fromdrug effects. These findings reveal that opiates andplacebo treatments both influence clinically relevant outcomes and operatewithoutmutual interference