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document
Paracetamol and opioid pathways : a pilot randomized clinical trial . Previous studies suggest that the antinociceptive action of paracetamol ( acetaminophen , APAP ) might involve descending inhibitory pain pathways and the opioidergic system : this study explores this issue in humans with naloxone , the opioid antagonist . After ethical approval , 12 healthy male volunteers were included in this randomized , controlled , double-blind , crossover , four-arm study . They were administered intravenous paracetamol ( APAP 1 g ) or saline ( placebo , pl ) followed at 100 min with IV naloxone ( Nal 8 mg ) or saline , every week for 4 weeks . The amplitude of cerebral potentials evoked by thermal/painful stimuli applied on the arm was recorded nine times over 150 min , witnessing of pain integration at central level . Amplitude changes as well as areas under the curve ( AUCs ) over 150 min were compared for the four treatments by repeated measures ANOVA ( significance 0.05 ) . Amplitude changes were significant for APAP/pl vs. pl/pl at t150 : -44 % ( 95 % CI -58 to -30 ) vs. -27 % ( 95 % CI -37 to -17 ; P < 0.05 ) but not vs. APAP/Nal . AUC ( 0-150 ) of APAP/pl is significantly different from pl/pl ( -3452 % .min ( 95 % CI -4705 to -2199 ) vs. -933 % min ( 95 % CI -2273 to 407 ; P = 0.015 ) but not from APAP/Nal ( -1731 % min ( 95 % CI -3676 to 214 ; P = 0.08 ) and other treatments . AUC ( 90-150 ) is not significantly different . This pilot study shows for the first time in human volunteers that naloxone does not inhibit paracetamol antinociception , suggesting no significant implication of the opioid system in paracetamol mechanism of action : this needs be confirmed on a larger number of subjects .
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Intervention_Pharmacological
Paracetamol
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Intervention_Pharmacological
paracetamol ( acetaminophen , APAP )
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Intervention_Pharmacological
naloxone
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Intervention_Pharmacological
opioid antagonist
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Intervention_Pharmacological
intravenous paracetamol
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Intervention_Control
saline
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Intervention_Control
placebo
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Intervention_Pharmacological
IV naloxone
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Intervention_Control
saline
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Intervention_Pharmacological
APAP/pl
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Intervention_Pharmacological
APAP/Nal
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Intervention_Pharmacological
APAP/Nal
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Intervention_Pharmacological
naloxone
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Intervention_Pharmacological
paracetamol
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Intervention_Pharmacological
paracetamol
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Outcome_Physical
amplitude of cerebral potentials evoked
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Outcome_Physical
Amplitude changes as well as areas under the curve ( AUCs )
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Outcome_Physical
Amplitude changes
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Outcome_Physical
AUC
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Outcome_Physical
AUC
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Outcome_Physical
inhibit paracetamol antinociception
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Participant_Sample-size
12
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Participant_Sample-size
male