Imaging human cerebral pain modulation by dose-dependent opioid analgesia: a positron emission tomography activation study using remifentanil.
BACKGROUND
Previous imaging studies have demonstrated a number of cortical and subcortical brain structures to be activated during noxious stimulation and infusion of narcotic analgesics. This study used O-water and positron emission tomography to investigate dose-dependent effects of the short-acting mu-selective opioid agonist remifentanil on regional cerebral blood flow during experimentally induced painful heat stimulation in healthy male volunteers.


METHODS
Positron emission tomography measurements were performed with injection of 7 mCi O-water during nonpainful heat and painful heat stimulation of the volar forearm. Three experimental conditions were used during both sensory stimuli: saline, 0.05 microg x kg x min remifentanil, and 0.15 microg x kg x min remifentanil. Cardiovascular and respiratory parameters were monitored noninvasively. Across the three conditions, dose-dependent effects of remifentanil on regional cerebral blood flow were analyzed on a pixel-wise basis using a statistical parametric mapping approach.


RESULTS
During saline infusion, regional cerebral blood flow increased in response to noxious thermal stimulation in a number of brain regions as previously reported. There was a reduction in pain-related activations with increasing doses of remifentanil in the thalamus, insula, and anterior and posterior cingulate cortex. Increasing activation occurred in the cingulofrontal cortex (including the perigenual anterior cingulate cortex) and the periaqueductal gray.


CONCLUSIONS
Remifentanil induced regional cerebral blood flow increases in the cingulofrontal cortex and periaqueductal gray during pain stimulation, indicating that mu-opioidergic activation modulates activity in pain inhibitory circuitries. This provides direct evidence that opioidergic analgesia is mediated by activation of established descending antinociceptive pathways.
Wagner
Klaus J
KJ
Klinik für Anaesthesiologie, Neurologische Klinik und Poliklinik, Technische Universität München, Klinikum rechts der Isar, Germany. klaus.wagner@lrz.tum.de
Sprenger
Till
T
Kochs
Eberhard F
EF
Tölle
Thomas R
TR
Valet
Michael
M
Willoch
Frode
F
D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D001784:Blood Gas Analysis / Q000379:methods; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001931:Brain Mapping / Q000379:methods; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation / Q000379:methods; D010880:Piperidines / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods; D012016:Reference Values; D000077208:Remifentanil; D012965:Sodium Chloride / Q000008:administration & dosage
D000701:Analgesics, Opioid; D010880:Piperidines; D012965:Sodium Chloride; D000077208:Remifentanil