Translational value of non-human primates in opioid research

Abstract

Preclinical opioid research using animal models not only provides mechanistic insights into the modulation of opioid analgesia and its associated side effects, but also validates drug candidates for improved treatment options for opioid use disorder. Non-human primates (NHPs) have served as a surrogate species for humans in opioid research for more than five decades. The translational value of NHP models is supported by the documented species differences between rodents and primates regarding their behavioral and physiological responses to opioid-related ligands and that NHP studies have provided more concordant results with human studies. This review highlights the utilization of NHP models in five aspects of opioid research, i.e., analgesia, abuse liability, respiratory depression, physical dependence, and pruritus. Recent NHP studies have found that (1) mixed mu opioid and nociceptin/orphanin FQ peptide receptor partial agonists appear to be safe, non-addictive analgesics and (2) mu opioid receptor- and mixed opioid receptor subtype-based medications remain the only two classes of drugs that are effective in alleviating opioid-induced adverse effects. Given the recent advances in pharmaceutical sciences and discoveries of novel targets, NHP studies are posed to identify the translational gap and validate therapeutic targets for the treatment of opioid use disorder. Pharmacological studies using NHPs along with multiple outcome measures (e.g., behavior, physiologic function, and neuroimaging) will continue to facilitate the research and development of improved medications to curb the opioid epidemic.

Keywords: Analgesia; Drug abuse; Itch; Macaque; Nociceptin/Orphanin FQ; Opioid receptor; Physical dependence; Respiratory depression; Spinal cord.

Figure 1.

Simplified scheme to summarize the functional profiles of two classes of opioid-related agonists based on human and/or non-human primate studies. + symbols represent the adverse effects associated with MOP receptor agonists. Dashed lines indicate reduced or lack of adverse effects associated with mixed MOP/NOP receptor partial agonists. ↓ symbols represent that the adverse effect can be ameliorated by a specific category of pharmacological agents.