Therapeutic potential of nociceptin/orphanin FQ peptide (NOP) receptor modulators for treatment of traumatic brain injury, traumatic stress, and their co-morbidities

The nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is a member of the opioid receptor superfamily with N/OFQ as its endogenous agonist. Wide expression of the NOP receptor and N/OFQ, both centrally and pe-ripherally, and their ability to modulate several biological functions has led to development of NOP receptor mod-ulators by pharmaceutical companies as therapeutics, based upon their efficacy in preclinical models of pain, anxiety, depression, Parkinson's disease, and substance abuse. Both posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are debilitating conditions that significantly affect the quality of life of millions of people around the world. PTSD is often a consequence of TBI, and, especially for those deployed to, working and/or living in a war zone or are first responders, they are comorbid. PTSD and TBI share common symptoms, and negatively influence outcomes as comorbidities of the other. Unfortunately, a lack of effective therapies or therapeutic agents limits the long term quality of life for either TBI or PTSD patients. Ours, and other groups, dem-onstrated that PTSD and TBI preclinical models elicit changes in the N/OFQ-NOP receptor system, and that admin-istration of NOP receptor ligands alleviated some of the neurobiological and behavioral changes induced by brain injury and/or traumatic stress exposure. Here we review the past and most recent progress on understanding the role of the N/OFQ-NOP receptor system in PTSD and TBI neurological and behavioral sequelae. There is still more to understand about this neuropeptide system in both PTSD and TBI, but current findings warrant further exam-ination of the potential utility of NOP modulators as therapeutics for these disorders and their co-morbidities. We advocate the development of standards for common data elements (CDE) reporting for preclinical PTSD studies, similar to current preclinical TBI CDEs. That would provide for more standardized data collection and reporting to improve reproducibility, interpretation and data sharing across studies. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

This article reviews the role of the N/OFQ-NOP receptor system in the neurological and behavioral sequelae of PTSD and TBI. The current findings suggest that NOP modulators may have potential as therapeutics for these disorders and their co-morbidities. The authors advocate for the development of standards for common data elements reporting to improve reproducibility and data sharing.