TY - JOUR

T1 - Prescription opioid analgesics rapidly change the human brain

AU - Younger, Jarred W

AU - Chu, Larry F

AU - D'Arcy, Nicole T

AU - Trott, Kiley E

AU - Jastrzab, Laura

AU - Mackey, Sean C

N1 - Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

PY - 2011/8

Y1 - 2011/8

N2 - Chronic opioid exposure is known to produce neuroplastic changes in animals; however, it is not known if opioids used over short periods of time and at analgesic dosages can similarly change brain structure in humans. In this longitudinal, magnetic resonance imaging study, 10 individuals with chronic low back pain were administered oral morphine daily for 1 month. High-resolution anatomical images of the brain were acquired immediately before and after the morphine administration period. Regional changes in gray matter volume were assessed on the whole brain using tensor-based morphometry, and those significant regional changes were then independently tested for correlation with morphine dosage. Thirteen regions evidenced significant volumetric change, and degree of change in several of the regions was correlated with morphine dosage. Dosage-correlated volumetric decrease was observed primarily in the right amygdala. Dosage-correlated volumetric increase was seen in the right hypothalamus, left inferior frontal gyrus, right ventral posterior cingulate, and right caudal pons. Follow-up scans that were conducted an average of 4.7 months after cessation of opioids demonstrated many of the morphine-induced changes to be persistent. In a separate study, 9 individuals consuming blinded placebo capsules for 6 weeks evidenced no significant morphologic changes over time. The results add to a growing body of literature showing that opioid exposure causes structural and functional changes in reward- and affect-processing circuitry. Morphologic changes occur rapidly in humans during new exposure to prescription opioid analgesics. Further research is needed to determine the clinical impact of those opioid-induced gray matter changes.

AB - Chronic opioid exposure is known to produce neuroplastic changes in animals; however, it is not known if opioids used over short periods of time and at analgesic dosages can similarly change brain structure in humans. In this longitudinal, magnetic resonance imaging study, 10 individuals with chronic low back pain were administered oral morphine daily for 1 month. High-resolution anatomical images of the brain were acquired immediately before and after the morphine administration period. Regional changes in gray matter volume were assessed on the whole brain using tensor-based morphometry, and those significant regional changes were then independently tested for correlation with morphine dosage. Thirteen regions evidenced significant volumetric change, and degree of change in several of the regions was correlated with morphine dosage. Dosage-correlated volumetric decrease was observed primarily in the right amygdala. Dosage-correlated volumetric increase was seen in the right hypothalamus, left inferior frontal gyrus, right ventral posterior cingulate, and right caudal pons. Follow-up scans that were conducted an average of 4.7 months after cessation of opioids demonstrated many of the morphine-induced changes to be persistent. In a separate study, 9 individuals consuming blinded placebo capsules for 6 weeks evidenced no significant morphologic changes over time. The results add to a growing body of literature showing that opioid exposure causes structural and functional changes in reward- and affect-processing circuitry. Morphologic changes occur rapidly in humans during new exposure to prescription opioid analgesics. Further research is needed to determine the clinical impact of those opioid-induced gray matter changes.

KW - Adolescent

KW - Adult

KW - Analgesics, Opioid/pharmacology

KW - Brain/drug effects

KW - Brain Mapping

KW - Dose-Response Relationship, Drug

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Image Processing, Computer-Assisted

KW - Low Back Pain/drug therapy

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Morphine/pharmacology

KW - Pain Measurement

KW - Prescription Drugs/pharmacology

KW - Statistics as Topic

KW - Young Adult

U2 - 10.1016/j.pain.2011.03.028

DO - 10.1016/j.pain.2011.03.028

M3 - Article

C2 - 21531077

VL - 152

SP - 1803

EP - 1810

JO - Pain

JF - Pain

SN - 0304-3959

IS - 8

ER -