title: Effective connectivity predicts future placebo analgesic response: A dynamic causal modeling study of pain processing in healthy controls.
abstract: A better understanding of the neural mechanisms underlying pain processing and analgesia may aid in the development and personalization of effective treatments for chronic pain. Clarification of the neural predictors of individual variability in placebo analgesia (PA) could aid in this process. The present study examined whether the strength of effective connectivity (EC) among pain-related brain regions could predict future placebo analgesic response in healthy individuals. In Visit 1, fMRI data were collected from 24 healthy subjects (13 females, mean age=22.56, SD=2.94) while experiencing painful thermal stimuli. During Visit 2, subjects were conditioned to expect less pain via a surreptitiously lowered temperature applied at two of the four sites on their feet. They were subsequently scanned again using the Visit 1 (painful) temperature. Subjects used an electronic VAS to rate their pain following each stimulus. Differences in ratings at conditioned and unconditioned sites were used to measure placebo response (PA scores). Dynamic causal modeling was used to estimate the EC among a set of brain regions related to pain processing at Visit 1 (periaqueductal gray, thalamus, rostral anterior cingulate cortex, dorsolateral prefrontal cortex). Individual PA scores from Visit 2 were regressed on salient EC parameter estimates from Visit 1. Results indicate that both greater left hemisphere modulatory DLPFC➔PAG connectivity and right hemisphere, endogenous thalamus➔DLPFC connectivity were significantly predictive of future placebo response (R(2)=0.82). To our knowledge, this is the first study to identify the value of EC in understanding individual differences in PA, and may suggest the potential modifiability of endogenous pain modulation.
authors: Department of Clinical & Health Psychology, College of Public Health and Health Professions, University of Florida, P.O. Box 100165, Gainesville, FL 32610-0165, USA.
authors: Landrew S
authors: LS
authors: Sevel
authors: Department of Clinical & Health Psychology, College of Public Health and Health Professions, University of Florida, P.O. Box 100165, Gainesville, FL 32610-0165, USA.
authors: Andrew M
authors: AM
authors: O'Shea
authors: Department of Clinical & Health Psychology, College of Public Health and Health Professions, University of Florida, P.O. Box 100165, Gainesville, FL 32610-0165, USA.
authors: Janelle E
authors: JE
authors: Letzen
authors: Department of Physical Therapy, School of Health Professions, University of Missouri, Columbia, 801 Clark Hall, MO 65211-4250, USA.
authors: Jason G
authors: JG
authors: Craggs
authors: Department of Oral & Maxillofacial Surgery, College of Dentistry, University of Florida, P.O. Box 100416, Gainesville, FL 32610-0416, USA.
authors: Donald D
authors: DD
authors: Price
authors: Department of Clinical & Health Psychology, College of Public Health and Health Professions, University of Florida, P.O. Box 100165, Gainesville, FL 32610-0165, USA. Electronic address: merobin@ufl.edu.
authors: Michael E
authors: ME
authors: Robinson
mesh_terms: D000698:Analgesia; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006358:Hot Temperature; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D010146:Pain / Q000503:physiopathology / Q000523:psychology*; D058748:Pain Perception / Q000502:physiology*; D015990:Placebo Effect; D055815:Young Adult
keywords: Dynamic causal modeling; Effective connectivity; Pain; Placebo analgesia; fMRI