N/OFQ-NOP System in Peripheral and Central Immunomodulation

  • Salim Kadhim
  • Mark F. Bird
  • David G. LambertEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 254)


Classical opioids (μ: mu, MOP; δ: delta, DOP and κ: kappa, KOP) variably affect immune function; they are immune depressants and there is good clinical evidence in the periphery. In addition, there is evidence for a central role in the control of a number of neuropathologies, e.g., neuropathic pain. Nociceptin/Orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ peptide receptor, NOP; peripheral and central activation can modulate immune function. In the periphery, NOP activation generally depresses immune function, but unlike classical opioids this is in part driven by NOP located on circulating immune cells. Peripheral activation has important implications in pathologies like asthma and sepsis. NOP is expressed on central neurones and glia where activation can modulate glial function. Microglia, as resident central ‘macrophages’, increase/infiltrate in pain and following trauma; these changes can be reduced by N/OFQ. Moreover, the interaction with other glial cell types such as the ubiquitous astrocytes and their known cross talk with microglia open a wealth of possibilities for central immunomodulation. At the whole animal level, clinical ligands with wide central and peripheral distribution have the potential to modulate immune function, and defining the precise nature of that interaction is important in mitigating or even harnessing the adverse effect profile of these important drugs.


Astrocytes Gliosis Immune function Lymphocytes Microglia N/OFQ receptor (NOP) Neuropathic pain Nociceptin/Orphanin FQ Sepsis 



Work on immune effects of opioids in Leicester is funded by Biotechnology and Biological Sciences Research Council and British Journal of Anaesthesia. SK is funded by a scholarship from Higher Committee for Education Development in Iraq.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Salim Kadhim
    • 1
  • Mark F. Bird
    • 1
  • David G. Lambert
    • 1
    Email author
  1. 1.Department of Cardiovascular Sciences, Anaesthesia Critical Care and Pain ManagementUniversity of Leicester, Leicester Royal InfirmaryLeicesterUK

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