Cutaneous amitriptyline in human volunteers: differential effects on the components of sensory information.
BACKGROUND
Amitriptyline is effective in relieving neuropathic pain. Its site of action is thought to be supraspinal and spinal, but a peripheral effect on fibers is also suggested.


METHODS
This double-blind study examined the effects of transcutaneous amitriptyline diluted in hydroalcoholic solution in healthy young male volunteers. Six treatments were randomly applied on different areas of the skin of the back: amitriptyline at 0 (vehicle), 25, 50, and 100 mm; saline (control); and lidocaine-prilocaine cream as a positive control. Up to 24 h after application, mechanical thresholds for touch and nociception, and thermal thresholds for cold, warm, and heat sensation were recorded for each area. Blood samples were collected to assess plasma levels of amitriptyline. A late recording of the tactile thresholds was performed 1 and 3 weeks after the treatment session.


RESULTS
The thresholds for all sensations did not differ between the vehicle and saline. Lidocaine-prilocaine cream displayed a short-lasting anesthetic effect for all sensations, although this was not significant for warm sensation. Amitriptyline, at the three concentrations studied, induced a mild and short-lasting increase of the tactile and mechanical nociceptive thresholds. It significantly decreased cold thresholds (down to 21.8 degrees C, P = 0.01 vs. 27.5 degrees C for control) and heat thresholds (down to 40.1 degrees C, P = 0.004 vs. 43.4 degrees C for control). These two effects were no longer significant after the fourth hour of observation. Amitriptyline did not change warm thresholds. There was no apparent systemic absorption effect of the drug.


CONCLUSIONS
It is hypothesized that amitriptyline has a differential effect on different fiber structures.
Dualé
Christian
C
Centre Hospitalier Universitaire (CHU) Clermont-Ferrand, Service d'Anesthésie-Réanimation, Hôpital Gabriel-Montpied, France. cduale@chu-clermontferrand.fr
Daveau
Julie
J
Cardot
Jean-Michel
JM
Boyer-Grand
Anne
A
Schoeffler
Pierre
P
Dubray
Claude
C
D000287:Administration, Topical; D000328:Adult; D000639:Amitriptyline / Q000008:administration & dosage*; D004311:Double-Blind Method; D006805:Human Experimentation; D006801:Humans; D008297:Male; D012684:Sensory Thresholds / Q000187:drug effects* / Q000502:physiology; D012867:Skin / Q000187:drug effects*; D014110:Touch / Q000187:drug effects / Q000502:physiology
D000639:Amitriptyline