Evaluation of the antihyperalgesic effect of tapentadol in two human evoked pain models - the TapCapMentho pilot trial.
OBJECTIVE
Tapentadol is effective in the treatment of neuropathic and nociceptive pain and in acute and chronic pain conditions; two mechanisms combining opioid µ-receptor agonism and noradrenergic reuptake inhibition underlie its analgesic effect.


METHODS
With this single-center, placebo-controlled, double-blind, cross-over pilot-study, we investigated the antihyperalgesic effect of a single oral dose of 100 mg immediate-release tapentadol on thermal and mechanical hyperalgesia in two human models (i.e. 0.6 % topical capsaicin and 40% topical menthol) of evoked neuropathic pain signs in healthy volunteers.


RESULTS
No significant differences regarding experimentally induced heat or cold and mechanical (pinprick) hyperalgesia, as assessed by quantitative sensory testing, could be observed between a single dose of drug and placebo (thermal pain thresholds p>0.4, mechanical pain sensitivity p>0.1). Only few mild side effects of tapentadol were reported.


CONCLUSIONS
The discrepancy between pain models using healthy volunteers and drug trials under real acute and chronic pain conditions in patients as well as methodological aspects may have contributed to this result. The impact of these findings questions the general use of pain models as predictors for early decision making during drug development. The study was registered in ClinicalTrials.gov (NCT01615510).
a Division of Neurological Pain Research and Therapy, Department of Neurology , Christian-Albrechts-Universität Kiel , Kiel , Germany.
M
M
Förster
a Division of Neurological Pain Research and Therapy, Department of Neurology , Christian-Albrechts-Universität Kiel , Kiel , Germany.
S
S
Helfert
a Division of Neurological Pain Research and Therapy, Department of Neurology , Christian-Albrechts-Universität Kiel , Kiel , Germany.
R
R
Dierschke
a Division of Neurological Pain Research and Therapy, Department of Neurology , Christian-Albrechts-Universität Kiel , Kiel , Germany.
M
M
Großkopf
a Division of Neurological Pain Research and Therapy, Department of Neurology , Christian-Albrechts-Universität Kiel , Kiel , Germany.
P
P
Hüllemann
b StatConsult , Magdeburg , Germany.
T
T
Keller
a Division of Neurological Pain Research and Therapy, Department of Neurology , Christian-Albrechts-Universität Kiel , Kiel , Germany.
R
R
Baron
a Division of Neurological Pain Research and Therapy, Department of Neurology , Christian-Albrechts-Universität Kiel , Kiel , Germany.
A
A
Binder
D000328:Adult; D002211:Capsaicin / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017288:Pain Threshold; D010636:Phenols / Q000494:pharmacology*; D010865:Pilot Projects; D000077432:Tapentadol; D055815:Young Adult
D010636:Phenols; D000077432:Tapentadol; D002211:Capsaicin
Capsaicin; cold hyperalgesia; heat hyperalgesia; mechanical hyperalgesia; menthol; quantitative sensory testing