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 anonymous peer review
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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