Pharmacological profile of a novel nonhuman primate model of knee osteoarthritis

Abstract

A number of promising compounds developed in rodent arthritis models lack efficacy in clinical osteoarthritis (OA) pain. To enhance successful translation of preclinical findings, a nonhuman primate (NHP) model of knee OA was developed and characterized using behavioral assessments designed for use in the NHP. A unilateral medial meniscectomy (MMx) was performed and animals underwent an exercise regimen. Decreased ipsilateral knee pressure threshold, pressure “hyperalgesia”, and decreased ipsilateral weight bearing, suggestive of pain at rest were observed. The sensitivity of the pain-related behaviors to pharmacological manipulation was evaluated. A single dose of the opioid morphine reduced pain-related behaviors. Likewise, the serotonin-norepinephrine reuptake inhibitor duloxetine reduced pain-related behavior, and efficacy was similar to that of morphine. By contrast, the anticonvulsant pregabalin did not significantly affect pain-related behavior. Repeated dosing with the non-steroidal anti-inflammatory drug (NSAID) diclofenac reduced pain-related behaviors whereas repeated dosing with the NK1 receptor antagonist aprepitant did not. The drug effects observed in the NHP OA model mirror the efficacy observed clinically.