Antinociceptive effect of clinical analgesics in a nonhuman primate model of knee osteoarthritis

Abstract

A number of potential analgesic pharmacotherapies developed in preclinical osteoarthritis animal models have failed clinical trials. A possible basis for the lack of translation of preclinical findings to clinical efficacy is the use of a preclinical species that is distinct from that of humans. The current study tested clinical analgesics in a nonhuman primate model of knee osteoarthritis. Following a medial meniscectomy, the animals developed a robust ipsilateral reduction in knee pressure threshold (hyperalgesia) and an ipsilateral reduction in weight bearing (resting pain). The serotonin-noradrenalin reuptake inhibitor duloxetine and opioid morphine increased ipsilateral pressure threshold and weight bearing. By contrast, the anticonvulsant pregabalin did not affect either pressure hyperalgesia or resting pain. The current findings in the nonhuman primate model of osteoarthritis parallel clinical findings, in that duloxetine and opioids are used in the management of osteoarthritis pain whereas pregabalin is not. The current findings also suggest the possible differentiation of pharmacotherapeutics in a nonhuman primate model, of distinguishing potential clinically useful analgesics for the management of osteoarthritic pain from those that are not.

Keywords: Cynomolgus macaque; Duloxetine HCl (PubChem CID: 60834); Hyperalgesia; Morphine HCl (PubChem CID: 5464110); Osteoarthritis; Target validation; Translational research; pregabalin (PubChem CID: 5486971).