Evaluation of the antihyperalgesic effect of tapentadol in two human evoked pain models – the TapCapMentho pilot trial

ABSTRACT

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.

Research design and 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).

KEYWORDS:

• Capsaicin
• cold hyperalgesia
• heat hyperalgesia
• mechanical hyperalgesia
• menthol
• quantitative sensory testing

Acknowledgments

This study was supported by a financial grant from Grünenthal Germany. The statistical analysis was performed by StatConsult, Magdeburg, Germany (www.statconsult.de).

Declaration of interest

This study was supported by Grünenthal within an Investigator Initiated Trial (IIT). The authors declare that the sources of financial support had no influence on data assessment, analysis and interpretation. All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: M Förster received honoraria from Pfizer and Grünenthal. S Helfert received honoraria Astellas, Genzyme, Pfizer and Grünenthal. P Hüllemann has received speaking fees from Pfizer and Genzyme and travel reimbursement from Grünenthal. T Keller received honoraria from Grünenthal for statistical analyses of other projects of Grünenthal. R Baron received support for travel from the BMBF, has consultancies with and received honoraria and travel/accommodation: Novartis, Biogen Idec, Astra Zeneca, Bristol-Myers Squibb, Teva, Bayer-Schering, AbbVie, Merck Sharp & Dohme, Merck, Daiichi-Sankyo, Glenmark, bioCSL, Genentech, received grants from Mundipharma. A Binder received honoraria for lectures from Grünenthal, Genzyme, Boehringer, Allergan and Pfizer, honoraria for consultancies from Genzyme, Grünenthal, Pfizer, Boehringer, and payment for development of educational presentations from Pfizer and travel/accommodation expenses from Pfizer, Allergan and Grünenthal. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Supplementary material

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Additional information

Funding

This research was made possible by the support of Grünenthal GmbH.