Non Opioid Treatment for Experimental Dyspnea (Nefopel)

The purpose of this protocol is to test the effects of the non opioid nefopam on experimental dyspnea and on the counterirritation (ie inhibition of one pain by another pain) induced by dyspnea in healthy subjects.

Dyspnea and pain share many features. One of them is the counterirritation phenomenon: defined in pain research as the attenuation of one pain by another pain. Dyspnea induced with inspiratory threshold loading (increased sense of work/effort ) has been shown to attenuate electrical pain as shown through nociceptive flexion reflex inhibition, or thermal pain, as measured with cortical evoked responses (laser evoked potentials-LEP). The investigators will study whether nefopam modulates the counterirritation of laboratory induced dyspnea in healthy subjects. The effect of nefopam on experimental dyspnea will be measured with a visual analog scale (VAS) and a validated multidimensional dyspnea profile (MDP). The effect of treatment on counterirritation will be measured by recording LEP obtained using a CO2 laser system. The amplitude of the N2-P2 component of the LEP is the main study outcome.

Subjects will be infused intravenously with nefopam (20mg/2mL) over a course of 30 minutes in a supine position. There will be a single administration of IV 20 mg nefopam and IV placebo. Each intervention will occur on a separate day.

variation of N2-P2 (components of laser evoked potential - tool of pain measurement)amplitude with inspiratory loading induced by intervention

LEP will be recorded before intervention at baseline and after intervention at baseline, during inspiratory loading and recovery. The outcome is the variation of N2-P2 amplitude with inspiratory loading induced by intervention

variation of N20-P25 amplitude (components of somesthesic evoked potential (SEP) -measurement of sensitivity)

SEP will be recorded before intervention at baseline and after intervention at baseline, during inspiratory loading. This is a methodological control

Inclusion Criteria: Healthy Non-smoking Exclusion Criteria: acute or chronic pain antalgic or psychoactive drugs use nefopam hypersensibility severe allergy diabetes glaucoma prostate adenoma seizure disorder or convulsion history heart or circulation disease pulmonary disease or asthma kidney or liver disease brain or nerve disease lack of adhesion to no antalgic drug, alcohol, coffee and cola within previous experiment day consumption