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

Abstract

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

Keywords

• pain
• opioid
• translatable
• monkey
• thermode
• noxious heat