Traumatic Brain Injury Induces Nociceptin/Orphanin FQ and Nociceptin Opioid Peptide Receptor Expression within 24 Hours

Int J Mol Sci. 2024 Jan 29;25(3):1658. doi: 10.3390/ijms25031658.


Traumatic brain injury (TBI) is a major cause of mortality and disability around the world, for which no treatment has been found. Nociceptin/Orphanin FQ (N/OFQ) and the nociceptin opioid peptide (NOP) receptor are rapidly increased in response to fluid percussion, stab injury, and controlled cortical impact (CCI) TBI. TBI-induced upregulation of N/OFQ contributes to cerebrovascular impairment, increased excitotoxicity, and neurobehavioral deficits. Our objective was to identify changes in N/OFQ and NOP receptor peptide, protein, and mRNA relative to the expression of injury markers and extracellular regulated kinase (ERK) 24 h following mild (mTBI) and moderate TBI (ModTBI) in wildtype (WT) and NOP receptor-knockout (KO) rats. N/OFQ was quantified by radioimmunoassay, mRNA expression was assessed using real-time PCR and protein levels were determined by immunoblot analysis. This study revealed increased N/OFQ mRNA and peptide levels in the CSF and ipsilateral tissue of WT, but not KO, rats 24 h post-TBI; NOP receptor mRNA increased after ModTBI. Cofilin-1 activation increased in the brain tissue of WT but not KO rats, ERK activation increased in all rats following ModTBI; no changes in injury marker levels were noted in brain tissue at this time. In conclusion, this study elucidates transcriptional and translational changes in the N/OFQ-NOP receptor system relative to TBI-induced neurological deficits and initiation of signaling cascades that support the investigation of the NOP receptor as a therapeutic target for TBI.

Keywords: cofilin-1; controlled cortical impact; injury severity; knockout rat; mitogen-activated protein kinases; nociceptin opioid peptide (NOP) receptor; nociceptin/orphanin FQ (N/OFQ); traumatic brain injury.

MeSH terms

  • Analgesics, Opioid
  • Animals
  • Brain Injuries, Traumatic* / genetics
  • Nociceptin Receptor*
  • Nociceptin*
  • Opioid Peptides / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Opioid / metabolism


  • Analgesics, Opioid
  • Nociceptin
  • Nociceptin Receptor
  • Opioid Peptides
  • Receptors, Opioid
  • RNA, Messenger