Functional magnetic resonance imaging studies of opioid receptor-mediated modulation of noxious-evoked BOLD contrast in rats.
BACKGROUND
Functional magnetic resonance imaging (fMRI) in rats can non-invasively identify brain regions activated by physiological stimuli and the effects of pharmacological intervention on these responses.


OBJECTIVE
This study was conducted to investigate the effects of systemic administration of the mu-opioid receptor agonist morphine on whole brain functional signal intensity in anaesthetised rats; to investigate whether pre-treatment with the opioid receptor antagonist naloxone blocks the effects of morphine; to determine whether pre-treatment with morphine attenuates noxious-evoked changes in whole brain functional signal intensity.


METHODS
Continuous whole brain fMRI scanning was used to study brain signal intensity prior to, and following, systemic administration of morphine (5 mg/kg, n=7), systemic administration of naloxone (1 mg/kg) and morphine (n=8). Effects of pre-treatment with saline (n=5) or morphine (5 mg/kg, n=5) on formalin (5%, intraplantar)-evoked changes in signal intensity were determined. Data were processed using SMP99 with fixed-effects analysis (p<0.05).


RESULTS
Morphine produced significant positive bilateral increases in signal intensity in the cingulate cortex, amygdala, thalamus, hypothalamus and PAG (p<0.05), and these effects were blocked by naloxone. Intraplantar injection of formalin produced a significant positive increase in signal intensity in the cingulate cortex, somatosensory cortex, amygdala, thalamus, hypothalamus and PAG (p<0.05). Morphine attenuated formalin-evoked increases in signal intensity in the PAG, amygdala, hypothalamus and cingulate cortex.


CONCLUSIONS
Our data demonstrate that morphine modulates noxious-evoked changes in signal intensity in discrete brain regions. fMRI studies in rats are able to identify specific brain regions involved in the pharmacological modification of physiologically evoked changes in regional brain activation.
Shah
Y B
YB
E. Floor Medical School, School of Biomedical Sciences, Sir Peter Mansfield Centre of Magnetic Resonance, University of Nottingham, Nottingham, NG72UH, UK.
Haynes
L
L
Prior
M J W
MJ
Marsden
C A
CA
Morris
P G
PG
Chapman
V
V
D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D004347:Drug Interactions; D005557:Formaldehyde / Q000009:adverse effects; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011957:Receptors, Opioid / Q000502:physiology*
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D005557:Formaldehyde; D009270:Naloxone; D009020:Morphine