共 38 条
Opioid Specific Effects on Central Processing of Sensation and Pain: A Randomized, Cross-Over, Placebo-Controlled Study
被引:4
作者:
Lelic, Dina
[1
]
Olesen, Anne Estrup
[1
,2
,3
]
Gronlund, Debbie
[1
,2
]
Jure, Fabricio Ariel
[4
]
Drewes, Asbjorn Mohr
[1
,2
]
机构:
[1] Aalborg Univ Hosp, Dept Gastroenterol & Hepatol, Mech Sense, Molleparkvej 4, DK-9000 Aalborg, Denmark
[2] Aalborg Univ, Dept Clin Med, Aalborg, Denmark
[3] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Copenhagen, Denmark
[4] Aalborg Univ, Ctr Sensory Motor Interact, Dept Hlth Sci & Technol, Integrat Neurosci, Aalborg, Denmark
关键词:
Morphine;
naloxone;
electroencephalography;
pupillometry;
QST;
NOCICEPTIVE WITHDRAWAL REFLEX;
EVOKED-POTENTIALS;
CINGULATE CORTEX;
FLEXION REFLEX;
TONIC PAIN;
MORPHINE;
MODULATION;
ANALGESIA;
OXYCODONE;
STIMULATION;
D O I:
10.1016/j.jpain.2021.06.011
中图分类号:
R74 [神经病学与精神病学];
学科分类号:
摘要:
Moderate to severe pain is often treated with opioids, but central mechanisms underlying opioid analgesia are poorly understood. Findings thus far have been contradictory and none could infer opioid specific effects. This placebo-controlled, randomized, 2-way crossover, double-blinded study aimed to explore opioid specific effects on central processing of external stimuli. Twenty healthy male volunteers were included and 3 sets of assessments were done at each of the 2 visits: 1) baseline, 2) during continuous morphine or placebo intravenous infusion and 3) during simultaneous morphine + naloxone or placebo infusion. Opioid antagonist naloxone was introduced in order to investigate opioid specific effects by observing which morphine effects are reversed by this intervention. Quantitative sensory testing, spinal nociceptive withdrawal reflexes (NWR), spinal electroencephalography (EEG), cortical EEG responses to external stimuli and resting EEG were measured and analyzed. Longer lasting pain (cold-pressor test - hand in 2 degrees water for 2 minutes, tetanic electrical), deeper structure pain (bone pressure) and strong nociceptive (NWR) stimulations were the most sensitive quantitative sensory testing measures of opioid analgesia. In line with this, the principal opioid specific central changes were seen in NWRs, EEG responses to NWRs and cold-pressor EEG. The magnitude of NWRs together with amplitudes and insular source strengths of the corresponding EEG responses were attenuated. The decreases in EEG activity were correlated to subjective unpleasantness scores. Brain activity underlying slow cold-pressor EEG (1-4Hz) was decreased, whereas the brain activity underlying faster EEG (8-12Hz) was increased. These changes were strongly correlated to subjective pain relief. This study points to evidence of opioid specific effects on perception of external stimuli and the underlying central responses. The analgesic response to opioids is likely a synergy of opioids acting at both spinal and supra-spinal levels of the central nervous system. Due to the strong correlations with pain relief, the changes in EEG signals during cold-pressor test have the potential to serve as biomarkers of opioid analgesia. Perspective: This exploratory study presents evidence of opioid specific effects on the pain system at peripheral and central levels. The findings give insights into which measures are the most sensitive for assessing opioid-specific effects. (C) 2021 by United States Association for the Study of Pain, Inc.
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页码:1477 / 1496
页数:20
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