TY - JOUR
T1 - Effective connectivity predicts future placebo analgesic response
T2 - A dynamic causal modeling study of pain processing in healthy controls
AU - Sevel, Landrew S.
AU - O'Shea, Andrew M.
AU - Letzen, Janelle E.
AU - Craggs, Jason G.
AU - Price, Donald D.
AU - Robinson, Michael E.
N1 - Funding Information:
This study was supported by grants from the National Center for Complementary and Alternative Medicine to Dr. Michael E. Robinson ( R01AT001424-05A2 )
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/4/5
Y1 - 2015/4/5
N2 - 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 (R2=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.
AB - 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 (R2=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.
KW - Dynamic causal modeling
KW - Effective connectivity
KW - FMRI
KW - Pain
KW - Placebo analgesia
UR - http://www.scopus.com/inward/record.url?scp=84922569354&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922569354&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2015.01.056
DO - 10.1016/j.neuroimage.2015.01.056
M3 - Article
C2 - 25659463
AN - SCOPUS:84922569354
SN - 1053-8119
VL - 110
SP - 87
EP - 94
JO - NeuroImage
JF - NeuroImage
ER -