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Pharmacological validation of a novel nonhuman primate measure of thermal responsivity with utility for predicting analgesic effects

Authors Vardigan JD, Houghton AK, Lange HS, Adarayan ED, Pall PS, Ballard JE, Henze DA, Uslaner JM

Received 29 September 2017

Accepted for publication 7 February 2018

Published 11 April 2018 Volume 2018:11 Pages 735—741

DOI https://doi.org/10.2147/JPR.S152879

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 3

Editor who approved publication: Dr Katherine Hanlon


Joshua D Vardigan, Andrea K Houghton, Henry S Lange, Emily D Adarayan, Parul S Pall, Jeanine E Ballard, Darrell A Henze, Jason M Uslaner

Merck Research Laboratories, West Point, PA, USA

Introduction: The development of novel analgesics to treat acute or chronic pain has been a challenge due to a lack of translatable measurements. Preclinical end points with improved translatability are necessary to more accurately inform clinical testing paradigms, which may help guide selection of viable drug candidates.
Methods: In this study, a nonhuman primate biomarker which is sensitive to standard analgesics at clinically relevant plasma concentrations, can differentiate analgesia from sedation and utilizes a protocol very similar to that which can be employed in human clinical studies is described. Specifically, acute heat stimuli were delivered to the volar forearm using a contact heat thermode in the same manner as the clinical setting.
Results: Clinically efficacious exposures of morphine, fentanyl, and tramadol produced robust analgesic effects, whereas doses of diazepam that produce sedation had no effect.
Conclusion: We propose that this assay has predictive utility that can help improve the probability of success for developing novel analgesics.

Keywords: pain, opioid, translatable, monkey, thermode, noxious heat

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