Pharmacological validation of a novel nonhuman primate measure of thermal responsivity with utility for predicting analgesic effects
Received 29 September 2017
Accepted for publication 7 February 2018
Published 11 April 2018 Volume 2018:11 Pages 735—741
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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]