Dissociable influences of opiates and expectations on pain.
Placebo treatments and opiate drugs are thought to have common effects on the opioid system and pain-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 relationship between expectations and opioid analgesia. We administered the opioid agonist remifentanil to human subjects during experimental 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, expectancy modulated activity in frontal cortex, with a separable time course from drug effects. These findings reveal that opiates and placebo treatments both influence clinically relevant outcomes and operate without mutual interference.
Department of Psychology, New York University, New York, New York 10003, USA. laurenatlas@nyu.edu
Lauren Y
LY
Atlas
Robert A
RA
Whittington
Martin A
MA
Lindquist
Joe
J
Wielgosz
Nomita
N
Sonty
Tor D
TD
Wager
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D059031:Anticipation, Psychological / Q000187:drug effects*; D001519:Behavior / Q000187:drug effects; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D010146:Pain / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000077208:Remifentanil; D055815:Young Adult
D000701:Analgesics, Opioid; D010880:Piperidines; D000077208:Remifentanil