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 peripherally, and their ability to modulate several biological functions has led to development of NOP receptor modulators 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, demonstrated that
PTSD and TBI preclinical models elicit changes in the N/OFQ-NOP receptor system, and that administration 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 examination 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.