Local Anaesthetic Effects of Transcutaneous Amitriptyline

Sixteen male healthy volunteers are enrolled for this study. They receive in a randomised order on six regions of dorsal skin (after previous targetting by ink marks) the six following treatments : lidocaïne-prilocaïne anaesthetic cream (EMLA (R)), normal saline, amityptiline hydrochloride diluted in solution of water (%), isopropanol (%) , glycerol (%), titrated with sodium hydroxide for pH=8.5, at four different concentrations (0,25, 50 and 100 mM). The person in charge of local application does not participate to further examination. Immediately after one hour of application, the volunteer is examined, and then every 2 hours during 8 hours, and 24 hours after the end if application. Every trial includes, for every treated area, (a) measurement of sensitive and nociceptive threshold to Von Frey hair application, (b) assessment of sensation induced by cold and heat after Rolltemp TM application, (c) measurement of sensitive threshold to cold, then sensitive and nociceptive thresholds to heat with Thermotest TM, (d) clinical evaluation of tolerance to the treatment, (e) blood sampling for measuring amitriptylinemia (HPLC). The possible residual anaesthetic effects of the treatment are assessed one and three weeks after the application, by measurement of sensitive and nociceptive threshold to Von Frey hair application. The statistical analysis will use two-way ANOVA, considering the following factors : treatment, time, order, subject, subject/order.