Specific effect of venlafaxine on single and repetitive experimental painful stimuli in humans.
BACKGROUND
Tricyclic antidepressants relieve neuropathic pain, and the analgesic properties of tricyclic antidepressants are substantiated in human experimental pain models. It has been speculated that drugs with a selective inhibition of presynaptic reuptake of both serotonin and noradrenaline could have an analgesic effect comparable to the analgesic effect of tricyclic antidepressants.


OBJECTIVE
Our objective was to evaluate the analgesic effect of the serotonin-noradrenaline reuptake inhibitor venlafaxine in human experimental pain models.


METHODS
The study was carried out as a randomized, placebo-controlled, double-blind, crossover experiment that included 16 healthy volunteers. A 37.5-mg dose of venlafaxine was given orally 4 times with 12-hour intervals, and pain tests were performed before and 3 hours after the second and fourth doses. Pain tests included the determination of pain detection and tolerance thresholds to pressure, pain detection and tolerance thresholds on single electrical transcutaneous stimulation of the sural nerve, pain temporal summation on repetitive electrical sural nerve stimulation, and pain experienced during the cold pressor test.


RESULTS
Venlafaxine increased thresholds for pain tolerance after single electrical stimulation (P =.005) and pain summation (P =.01) on repetitive stimulation but did not alter the thresholds for pain detection after single electrical sural nerve stimulation. Venlafaxine did not alter pain experienced during the cold pressor test or increase the pressure pain thresholds.


CONCLUSIONS
Venlafaxine increases the pain tolerance threshold to electrical sural nerve stimulation and the threshold at which pain increases (pain summation). The impact of venlafaxine on pain summation in this experimental pain model on repetitive stimulation may indicate a potential analgesic effect for clinical neuropathic pain.
Enggaard
T P
TP
Institute of Public Health, Clinical Pharmacology, University of Southern Denmark-Main campus, Odense University, Denmark.
Klitgaard
N A
NA
Gram
L F
LF
Arendt-Nielsen
L
L
Sindrup
S H
SH
D000328:Adult; D000700:Analgesics / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D003080:Cold Temperature; D018592:Cross-Over Studies; D003511:Cyclohexanols / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D011312:Pressure; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000069470:Venlafaxine Hydrochloride
D000700:Analgesics; D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride