Acetaminophen's Antinociceptive Effect When Associated With N-Acetylcysteneine

Period 1 : To Day -4 to Day 0

Day -4 at 8:00 am at Clinical Pharmacology Center

• Inclusion Visit, signature of Informed consent form, clinical exam.
• Training test
• Blood sample (GSH, pharmacogenetic, Biochemistry assay)
• Randomization and attribution of treatment for the fisrt study period at home: (day -4, -3, -2, -1) 4 days of oral acetaminophen and [N-acetylcysteine or placebo] according to the randomization plan.

At day -3, -2 and -1 a salivary sample will be done to control the treatment compliance.

Day 0 at Clinical Pharmacology Center Clinical examination Measurement of the basal pain thresholds and pain evaluation (Visual Analog Scales) Blood and urinary sample (acetaminophen and GSH assay)

T0 : Administration of product: acetaminophen and [N-acetylcysteine or placebo]

T0+1H: Thermal stimulation according to the established paradigm (threshold temperature +3°C ) and pain evaluation (Visual Analog Scales)

T0+2H: Thermal stimulation according to the established paradigm (threshold temperature +3°C ) and pain evaluation (Visual Analog Scales) and Blood sample (acetaminophen assay)

T0+3H: Thermal stimulation according to the established paradigm (threshold temperature +3°C ) and pain evaluation (Visual Analog Scales)

T0+4H: Thermal stimulation according to the established paradigm (threshold temperature +3°C ) and pain evaluation (Visual Analog Scales) and Blood and urinary sample (acetaminophen, GSH, biochemistry assay)

• Lunch before departure

2 weeks of wash-out

Period 2 : To Day 17 to Day 21

Same of period 1. Subject who receives N-acétylcystéine in period 1 will receive placebo in second period and vice versa.

Inclusion criteria

• Male
• Between 18 and 45 years old
• Without treatment during the 7 days before inclusion specially no use of antalgic and anti-inflammatory
• Cooperation and understanding enough to conform to the study obligations -Having given free, informed written consent
• Affiliated at system of French social security
• Inscription or acceptation of inscription in the national register of volunteers involved in trials.

Exclusion criteria

• Patient with one or many contraindication for the administration of the trial's products,
• Patient that have taken N-acetylcysteine as bronchial thinner during the last 3 days,
• Patient with medical or surgical history judged by the investigator or his representative as being not compatible with the clinical trial
• Patient with disease progression during inclusion,
• Patient with excessive consumption of alcohol, tobacco (+ than 10 cigarette/day), coffee, tea or drinks with caffeine (equivalent to more than 4 cup a day) or any addiction to drugs,
• Patient with a heat pain mean threshold during training higher or equal to 46.5°C,
• Patient who participated in another clinical trial, located in exclusion period or received benefits > 4500 euros during 12 months before the beginning of trial,
• Patient with cooperation and understanding that do not allow him to follow the trial,
• Patients with minor or under guardianship,
• No affiliation at system of French social security