Skip to main content
SpringerLink
Log in

N/OFQ-NOP System in Peripheral and Central Immunomodulation

  • Chapter
  • First Online:
The Nociceptin/Orphanin FQ Peptide Receptor

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 254))

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Acosta C, Davies A (2008) Bacterial lipopolysaccharide regulates nociceptin expression in sensory neurons. J Neurosci Res 86:1077–1086

    PubMed  CAS  Google Scholar 

  • Al-Hashimi M, Scott SW, Thompson JP, Lambert DG (2013) Opioids and immune modulation: more questions than answers. Br J Anaesth 111:80–88

    PubMed  CAS  Google Scholar 

  • Al-Hashimi M, McDonald J, Thompson JP, Lambert DG (2016) Evidence for nociceptin/orphanin FQ (NOP) but not micro (MOP), delta (DOP) or kappa (KOP) opioid receptor mRNA in whole human blood. Br J Anaesth 116:423–429

    PubMed  CAS  Google Scholar 

  • Alt C, Lam JS, Harrison MT, Kershaw KM, Samuelsson S, Toll L, D’Andrea A (2012) Nociceptin/orphanin FQ inhibition with SB612111 ameliorates dextran sodium sulfate-induced colitis. Eur J Pharmacol 683:285–293

    PubMed  PubMed Central  CAS  Google Scholar 

  • Araque A, Navarrete M (2010) Glial cells in neuronal network function. Philos Trans R Soc Lond B Biol Sci 365:2375–2381

    PubMed  PubMed Central  Google Scholar 

  • Arjomand J, Cole S, Evans CJ (2002) Novel orphanin FQ/nociceptin transcripts are expressed in human immune cells. J Neuroimmunol 130:100–108

    PubMed  CAS  Google Scholar 

  • Attwell D, Buchan AM, Charpak S, Lauritzen M, MacVicar BA, Newman EA (2010) Glial and neuronal control of brain blood flow. Nature 468:232–243

    PubMed  PubMed Central  CAS  Google Scholar 

  • Bailey MS, Shipley MT (1993) Astrocyte subtypes in the rat olfactory bulb: morphological heterogeneity and differential laminar distribution. J Comp Neurol 328:501–526

    PubMed  CAS  Google Scholar 

  • Bakiri Y, Burzomato V, Frugier G, Hamilton NB, Karadottir R, Attwell D (2009) Glutamatergic signaling in the brain’s white matter. Neuroscience 158:266–274

    PubMed  CAS  Google Scholar 

  • Basso M, Risse PA, Naline E, Calo G, Guerrini R, Regoli D, Advenier C (2005) Nociceptin/orphanin FQ inhibits electrically induced contractions of the human bronchus via NOP receptor activation. Peptides 26:1492–1496

    PubMed  CAS  Google Scholar 

  • Basu S, Dasgupta PS (2000) Dopamine, a neurotransmitter, influences the immune system. J Neuroimmunol 102:113–124

    PubMed  CAS  Google Scholar 

  • Bedini A, Baiula M, Vincelli G, Formaggio F, Lombardi S, Caprini M, Spampinato S (2017) Nociceptin/orphanin FQ antagonizes lipopolysaccharide-stimulated proliferation, migration and inflammatory signaling in human glioblastoma U87 cells. Biochem Pharmacol 140:89–104

    PubMed  CAS  Google Scholar 

  • Beggs S, Salter MW (2006) Neuropathic pain: symptoms, models, and mechanisms. Drug Dev Res 67:289–301

    CAS  Google Scholar 

  • Bidlack JM (2000) Detection and function of opioid receptors on cells from the immune system. Clin Diagn Lab Immunol 7:719

    PubMed  PubMed Central  CAS  Google Scholar 

  • Bird MF, Guerrini R, Willets JM, Thompson JP, Caló G, Lambert DG (2018) Nociceptin/Orphanin FQ (N/OFQ) conjugated to ATTO594; a novel fluorescent probe for the NOP receptor. Br J Pharmacol 175:4496

    PubMed  PubMed Central  CAS  Google Scholar 

  • Boddeke EWGM (2001) Involvement of chemokines in pain. Eur J Pharmacol 429:115–119

    PubMed  CAS  Google Scholar 

  • Bundgaard M, Abbott NJ (2008) All vertebrates started out with a glial blood-brain barrier 4–500 million years ago. Glia 56:699–708

    PubMed  Google Scholar 

  • Buzas B (2002) Regulation of nociceptin/orphanin FQ gene expression in astrocytes by ceramide. Neuroreport 13:1707–1710

    PubMed  CAS  Google Scholar 

  • Buzas B, Rosenberger J, Cox BM (1998) Activity and cyclic AMP-dependent regulation of nociceptin/orphanin FQ gene expression in primary neuronal and astrocyte cultures. J Neurochem 71:556–563

    PubMed  CAS  Google Scholar 

  • Cadet P, Mantione K, Bilfinger TV, Stefano GB (2001) Real-time RT-PCR measurement of the modulation of Mu opiate receptor expression by nitric oxide in human mononuclear cells. Med Sci Monit 7:1123–1128

    PubMed  CAS  Google Scholar 

  • Caldiroli E, Leoni O, Cattaneo S, Rasini E, Marino V, Tosetto C, Mazzone A, Fietta AM, Lecchini S, Frigo GM (1999) Neutrophil function and opioid receptor expression on leucocytes during chronic naltrexone treatment in humans. Pharmacol Res 40:153–158

    PubMed  CAS  Google Scholar 

  • Carare RO, Hawkes CA, Weller RO (2014) Afferent and efferent immunological pathways of the brain. Anatomy, function and failure. Brain Behav Immun 36:9–14

    PubMed  CAS  Google Scholar 

  • Carvalho D, Petronilho F, Vuolo F, Machado RA, Constantino L, Guerrini R, Calo G, Gavioli EC, Streck EL, Dal-Pizzol F (2008) The nociceptin/orphanin FQ-NOP receptor antagonist effects on an animal model of sepsis. Intensive Care Med 34:2284–2290

    PubMed  CAS  Google Scholar 

  • Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354:610–621

    PubMed  CAS  Google Scholar 

  • Colton CA, Wilcock DM (2010) Assessing activation states in microglia. CNS Neurol Disord Drug Targets 9:174–191

    PubMed  CAS  Google Scholar 

  • Cornell-Bell AH, Finkbeiner SM, Cooper MS, Smith SJ (1990) Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247:470–473

    PubMed  CAS  Google Scholar 

  • D’Addario C, Caputi FF, Ekström TJ, Di Benedetto M, Maccarrone M, Romualdi P, Candeletti S (2013) Ethanol induces epigenetic modulation of prodynorphin and pronociceptin gene expression in the rat amygdala complex. J Mol Neurosci 49:312–319

    PubMed  Google Scholar 

  • Davoust N, Vuaillat C, Androdias G, Nataf S (2008) From bone marrow to microglia: barriers and avenues. Trends Immunol 29:227–234

    PubMed  CAS  Google Scholar 

  • Devine DP, Watson SJ, Akil H (2001) Nociceptin/orphanin FQ regulates neuroendocrine function of the limbic–hypothalamic–pituitary–adrenal axis. Neuroscience 102:541–553

    PubMed  CAS  Google Scholar 

  • Eriksson KS, Stevens DR, Haas HL (2000) Opposite modulation of histaminergic neurons by nociceptin and morphine. Neuropharmacology 39:2492–2498

    PubMed  CAS  Google Scholar 

  • Eschenroeder AC, Vestal-Laborde AA, Sanchez ES, Robinson SE, Sato-Bigbee C (2012) Oligodendrocyte responses to buprenorphine uncover novel and opposing roles of μ-opioid-and nociceptin/orphanin FQ receptors in cell development: implications for drug addiction treatment during pregnancy. Glia 60:125–136

    PubMed  Google Scholar 

  • Finley MJ, Happel CM, Kaminsky DE, Rogers TJ (2008) Opioid and nociceptin receptors regulate cytokine and cytokine receptor expression. Cell Immunol 252:146–154

    PubMed  PubMed Central  CAS  Google Scholar 

  • Fiset ME, Gilbert C, Poubelle PE, Pouliot M (2003) Human neutrophils as a source of nociceptin: a novel link between pain and inflammation. Biochemistry 42:10498–10505

    PubMed  PubMed Central  CAS  Google Scholar 

  • Fu X, Zhu ZH, Wang YQ, Wu GC (2007) Regulation of proinflammatory cytokines gene expression by nociceptin/orphanin FQ in the spinal cord and the cultured astrocytes. Neuroscience 144:275–285

    PubMed  CAS  Google Scholar 

  • Galea I, Bechmann I, Perry VH (2007) What is immune privilege (not)? Trends Immunol 28:12–18

    PubMed  CAS  Google Scholar 

  • Giaume C, Kirchhoff F, Matute C, Reichenbach A, Verkhratsky A (2007) Glia: the fulcrum of brain diseases. Cell Death Differ 14:1324–1335

    PubMed  CAS  Google Scholar 

  • Gough H, Grabenhenrich L, Reich A, Eckers N, Nitsche O, Schramm D, Beschorner J, Hoffmann U, Schuster A, Bauer CP, Forster J, Zepp F, Lee YA, Bergmann RL, Bergmann KE, Wahn U, Lau S, Keil T (2015) Allergic multimorbidity of asthma, rhinitis and eczema over 20 years in the German birth cohort MAS. Pediatr Allergy Immunol 26:431–437

    PubMed  PubMed Central  Google Scholar 

  • Hald A, Nedergaard S, Hansen RR, Ding M, Heegaard AM (2009) Differential activation of spinal cord glial cells in murine models of neuropathic and cancer pain. Eur J Pain 13:138–145

    PubMed  CAS  Google Scholar 

  • Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, Wardlaw AJ, Green RH (2008) Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 178:218–224

    PubMed  PubMed Central  Google Scholar 

  • Hanisch U-K, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394

    PubMed  CAS  Google Scholar 

  • Herz J, Filiano AJ, Smith A, Yogev N, Kipnis J (2017) Myeloid cells in the central nervous system. Immunity 46:943–956

    PubMed  PubMed Central  CAS  Google Scholar 

  • Hom JS, Goldberg I, Mathis J, Pan YX, Brooks AI, Ryan-Moro J, Scheinberg DA, Pasternak GW (1999) [(125)I]orphanin FQ/nociceptin binding in Raji cells. Synapse 34:187–191

    PubMed  CAS  Google Scholar 

  • Hussey HH, Katz S (1950) Infections resulting from narcotic addiction: report of 102 cases. Am J Med 9:186–193

    PubMed  CAS  Google Scholar 

  • Hutchinson MR, Northcutt AL, Hiranita T, Wang X, Lewis SS, Thomas J, van Steeg K, Kopajtic TA, Loram LC, Sfregola C, Galer E, Miles NE, Bland ST, Amat J, Rozeske RR, Maslanik T, Chapman TR, Strand KA, Fleshner M, Bachtell RK, Somogyi AA, Yin H, Katz JL, Rice KC, Maier SF, Watkins LR (2012) Opioid activation of toll-like receptor 4 contributes to drug reinforcement. J Neurosci 32:11187–11200

    PubMed  PubMed Central  CAS  Google Scholar 

  • Inoue K, Tsuda M (2018) Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential. Nat Rev Neurosci 19:138

    PubMed  CAS  Google Scholar 

  • Ji R-R, Suter MR (2007) p38 MAPK, microglial signaling, and neuropathic pain. Mol Pain 3:33

    PubMed  PubMed Central  Google Scholar 

  • Jurewicz A, Matysiak M, Tybor K, Kilianek L, Raine CS, Selmaj K (2005) Tumour necrosis factor-induced death of adult human oligodendrocytes is mediated by apoptosis inducing factor. Brain 128:2675–2688

    PubMed  Google Scholar 

  • Kadhim S, McDonald J, Lambert D (2018a) Nociceptin/Orphanin FQ (NOP) receptor is differentially expressed on glial cells. Br J Anaesth 120:e6

    Google Scholar 

  • Kadhim S, McDonald J, Lambert DG (2018b) Opioids, gliosis and central immunomodulation. J Anesth 32:756–767

    PubMed  Google Scholar 

  • Kallupi M, Varodayan FP, Oleata CS, Correia D, Luu G, Roberto M (2014) Nociceptin/Orphanin FQ decreases glutamate transmission and blocks ethanol-induced effects in the central amygdala of naive and ethanol-dependent rats. Neuropsychopharmacology 39:1081–1092

    PubMed  CAS  Google Scholar 

  • Kappel M, Poulsen TD, Galbo H, Pedersen BK (1998) Effects of elevated plasma noradrenaline concentration on the immune system in humans. Eur J Appl Physiol Occup Physiol 79:93–98

    PubMed  CAS  Google Scholar 

  • Kato S, Tsuzuki Y, Hokari R, Okada Y, Miyazaki J, Matsuzaki K, Iwai A, Kawaguchi A, Nagao S, Itoh K, Suzuki H, Nabeshima T, Miura S (2005) Role of nociceptin/orphanin FQ (Noc/oFQ) in murine experimental colitis. J Neuroimmunol 161:21–28

    PubMed  CAS  Google Scholar 

  • Kettenmann H, Verkhratsky A (2008) Neuroglia: the 150 years after. Trends Neurosci 31:653–659

    PubMed  CAS  Google Scholar 

  • Kohno K, Kitano J, Kohro Y, Tozaki-Saitoh H, Inoue K, Tsuda M (2018) Temporal kinetics of microgliosis in the spinal dorsal horn after peripheral nerve injury in rodents. Biol Pharm Bull 41:1096–1102

    PubMed  CAS  Google Scholar 

  • Lai H-C, Lu C-H, Wong C-S, Lin B-F, Chan S-M, Kuo C-Y, Wu Z-F (2018) Baicalein attenuates neuropathic pain and improves sciatic nerve function recovery in rats with partial sciatic nerve transection. J Chin Med Assoc 81:955–963

    PubMed  Google Scholar 

  • Lambert DG (2008) The nociceptin/orphanin FQ receptor: a target with broad therapeutic potential. Nat Rev Drug Discov 7:694–710

    PubMed  CAS  Google Scholar 

  • Ledeboer A, Sloane EM, Milligan ED, Frank MG, Mahony JH, Maier SF, Watkins LR (2005) Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain 115:71–83

    PubMed  CAS  Google Scholar 

  • Lotvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, Lemanske RF Jr, Wardlaw AJ, Wenzel SE, Greenberger PA (2011) Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 127:355–360

    PubMed  Google Scholar 

  • Madden JJ, Whaley WL, Ketelsen D, Donahoe RM (2001) The morphine-binding site on human activated T-cells is not related to the mu opioid receptor. Drug Alcohol Depend 62:131–139

    PubMed  CAS  Google Scholar 

  • Magistretti PJ (2006) Neuron–glia metabolic coupling and plasticity. J Exp Biol 209:2304–2311

    PubMed  CAS  Google Scholar 

  • Manfredi B, Sacerdote P, Bianchi M, Locatelli L, Veljic-Radulovic J, Panerai AE (1993) Evidence for an opioid inhibitory effect on T cell proliferation. J Neuroimmunol 44:43–48

    PubMed  CAS  Google Scholar 

  • Marchand F, Perretti M, McMahon SB (2005) Role of the immune system in chronic pain. Nat Rev Neurosci 6:521–532

    PubMed  CAS  Google Scholar 

  • Marti M, Mela F, Veronesi C, Guerrini R, Salvadori S, Federici M, Mercuri NB, Rizzi A, Franchi G, Beani L (2004) Blockade of nociceptin/orphanin FQ receptor signaling in rat substantia nigra pars reticulata stimulates nigrostriatal dopaminergic transmission and motor behavior. J Neurosci 24:6659–6666

    PubMed  CAS  Google Scholar 

  • Marti M, Mela F, Fantin M, Zucchini S, Brown JM, Witta J, Di Benedetto M, Buzas B, Reinscheid RK, Salvadori S (2005) Blockade of nociceptin/orphanin FQ transmission attenuates symptoms and neurodegeneration associated with Parkinson’s disease. J Neurosci 25:9591–9601

    PubMed  CAS  Google Scholar 

  • Mattson MP, Chan SL (2003) Neuronal and glial calcium signaling in Alzheimer’s disease. Cell Calcium 34:385–397

    PubMed  CAS  Google Scholar 

  • Meis S, Pape HC (2001) Control of glutamate and GABA release by nociceptin/orphanin FQ in the rat lateral amygdala. J Physiol 532:701–712

    PubMed  PubMed Central  CAS  Google Scholar 

  • Meyer LC, Paisley CE, Mohamed E, Bigbee JW, Kordula T, Richard H, Lutfy K, Sato-Bigbee C (2017) Novel role of the nociceptin system as a regulator of glutamate transporter expression in developing astrocytes. Glia 65:2003–2023

    PubMed  PubMed Central  Google Scholar 

  • Minami M, Yamakuni H, Ohtani Y, Okada M, Nakamura J, Satoh M (2001) Leukemia inhibitory factor induces nociceptin mRNA in cultured rat cortical neurons. Neurosci Lett 311:17–20

    PubMed  CAS  Google Scholar 

  • Morgan EL (1996) Regulation of human B lymphocyte activation by opioid peptide hormones. Inhibition of IgG production by opioid receptor class (mu-, kappa-, and delta-) selective agonists. J Neuroimmunol 65:21–30

    PubMed  CAS  Google Scholar 

  • Mulligan SJ, MacVicar BA (2004) Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature 431:195–199

    PubMed  CAS  Google Scholar 

  • Murphy NP, Maidment NT (1999) Orphanin FQ/nociceptin modulation of mesolimbic dopamine transmission determined by microdialysis. J Neurochem 73:179–186

    PubMed  CAS  Google Scholar 

  • Murphy NP, Ly HT, Maidment NT (1996) Intracerebroventricular orphanin FQ/nociceptin suppresses dopamine release in the nucleus accumbens of anaesthetized rats. Neuroscience 75:1–4

    PubMed  CAS  Google Scholar 

  • Nakano K, Matsushita S, Saito K, Yamaoka K, Tanaka Y (2009) Dopamine as an immune-modulator between dendritic cells and T cells and the role of dopamine in the pathogenesis of rheumatoid arthritis. Nihon Rinsho Meneki Gakkai Kaishi 32:1–6

    PubMed  CAS  Google Scholar 

  • Nedergaard M, Ransom B, Goldman SA (2003) New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci 26:523–530

    PubMed  CAS  Google Scholar 

  • Nicol B, Lambert DG, Rowbotham DJ, Smart D, McKnight AT (1996) Nociceptin induced inhibition of K+ evoked glutamate release from rat cerebrocortical slices. Br J Pharmacol 119:1081–1083

    PubMed  PubMed Central  CAS  Google Scholar 

  • Oh SB, Tran PB, Gillard SE, Hurley RW, Hammond DL, Miller RJ (2001) Chemokines and glycoprotein120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J Neurosci 21:5027–5035

    PubMed  CAS  Google Scholar 

  • Peluso J, LaForge KS, Matthes HW, Kreek MJ, Kieffer BL, Gavériaux-Ruff C (1998) Distribution of nociceptin/orphanin FQ receptor transcript in human central nervous system and immune cells. J Neuroimmunol 81:184–192

    PubMed  CAS  Google Scholar 

  • Pettersson LM, Sundler F, Danielsen N (2002) Expression of orphanin FQ/nociceptin and its receptor in rat peripheral ganglia and spinal cord. Brain Res 945:266–275

    PubMed  CAS  Google Scholar 

  • Popiolek-Barczyk K, Rojewska E, Jurga AM, Makuch W, Zador F, Borsodi A, Piotrowska A, Przewlocka B, Mika J (2014) Minocycline enhances the effectiveness of nociceptin/orphanin FQ during neuropathic pain. Biomed Res Int 2014:762930

    PubMed  PubMed Central  Google Scholar 

  • Powell EM, Geller HM (1999) Dissection of astrocyte-mediated cues in neuronal guidance and process extension. Glia 26:73–83

    PubMed  CAS  Google Scholar 

  • Raff MC, Abney ER, Cohen J, Lindsay R, Noble M (1983) Two types of astrocytes in cultures of developing rat white matter: differences in morphology, surface gangliosides, and growth characteristics. J Neurosci 3:1289–1300

    PubMed  CAS  Google Scholar 

  • Raghavendra V, Tanga F, DeLeo JA (2003) Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J Pharmacol Exp Ther 306:624–630

    PubMed  CAS  Google Scholar 

  • Ramesh G, Benge S, Pahar B, Philipp MT (2012) A possible role for inflammation in mediating apoptosis of oligodendrocytes as induced by the Lyme disease spirochete Borrelia burgdorferi. J Neuroinflammation 9:72

    PubMed  PubMed Central  CAS  Google Scholar 

  • Raper D, Louveau A, Kipnis J (2016) How do meningeal lymphatic vessels drain the CNS? Trends Neurosci 39:581–586

    PubMed  PubMed Central  CAS  Google Scholar 

  • Scholz J, Woolf CJ (2007) The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 10:1361

    PubMed  CAS  Google Scholar 

  • Seifert G, Schilling K, Steinhäuser C (2006) Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat Rev Neurosci 7:194

    PubMed  CAS  Google Scholar 

  • Serhan CN, Fierro IM, Chiang N, Pouliot M (2001) Cutting edge: nociceptin stimulates neutrophil chemotaxis and recruitment: inhibition by aspirin-triggered-15-epi-lipoxin A4. J Immunol 166:3650–3654

    PubMed  CAS  Google Scholar 

  • Shah S, Page CP, Spina D (1998) Nociceptin inhibits non-adrenergic non-cholinergic contraction in guinea-pig airway. Br J Pharmacol 125:510–516

    PubMed  PubMed Central  CAS  Google Scholar 

  • Singh S, Sullo N, Bradding P, Agostino B, Brightling C, Lambert D (2013) Role of nociceptin orphanin FQ peptide – receptor system in mast cell migration. Eur Respir J 42:P587

    Google Scholar 

  • Singh SR, Sullo N, Matteis M, Spaziano G, McDonald J, Saunders R, Woodman L, Urbanek K, De Angelis A, De Palma R, Berair R, Pancholi M, Mistry V, Rossi F, Guerrini R, Calò G, D’Agostino B, Brightling CE, Lambert DG (2016) Nociceptin/orphanin FQ (N/OFQ) modulates immunopathology and airway hyperresponsiveness representing a novel target for the treatment of asthma. Br J Pharmacol 173:1286–1301

    PubMed  PubMed Central  CAS  Google Scholar 

  • Smith K (2010) Neuroscience: settling the great glia debate. Nature 468:160–162

    PubMed  CAS  Google Scholar 

  • Stamer UM, Book M, Comos C, Zhang L, Nauck F, Stüber F (2011) Expression of the nociceptin precursor and nociceptin receptor is modulated in cancer and septic patients. Br J Anaesth 106:566–572

    PubMed  CAS  Google Scholar 

  • Tanga FY, Raghavendra V, DeLeo JA (2004) Quantitative real-time RT-PCR assessment of spinal microglial and astrocytic activation markers in a rat model of neuropathic pain. Neurochem Int 45:397–407

    PubMed  CAS  Google Scholar 

  • Thomas R, Stover C, Lambert DG, Thompson JP (2014) Nociceptin system as a target in sepsis? J Anesth 28:759–767

    PubMed  Google Scholar 

  • Thompson JP, Serrano-Gomez A, McDonald J, Ladak N, Bowrey S, Lambert DG (2013) The Nociceptin/Orphanin FQ system is modulated in patients admitted to ICU with sepsis and after cardiopulmonary bypass. PLoS One 8:e76682

    PubMed  PubMed Central  CAS  Google Scholar 

  • Trombella S, Vergura R, Falzarano S, Guerrini R, Calo G, Spisani S (2005) Nociceptin/orphanin FQ stimulates human monocyte chemotaxis via NOP receptor activation. Peptides 26:1497–1502

    PubMed  CAS  Google Scholar 

  • Tsao C-W, Lin Y-S, Cheng J-T (1997) Effect of dopamine on immune cell proliferation in mice. Life Sci 61:PL361–PL371

    CAS  Google Scholar 

  • Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6:626

    PubMed  CAS  Google Scholar 

  • Watkins LR, Maier SF (2000) The pain of being sick: implications of immune-to-brain communication for understanding pain. Annu Rev Psychol 51:29–57

    PubMed  CAS  Google Scholar 

  • Watkins LR, Milligan ED, Maier SF (2001) Glial activation: a driving force for pathological pain. Trends Neurosci 24:450–455

    PubMed  CAS  Google Scholar 

  • Wick MJ, Minnerath SR, Roy S, Ramakrishnan S, Loh HH (1995) Expression of alternate forms of brain opioid ‘orphan’ receptor mRNA in activated human peripheral blood lymphocytes and lymphocytic cell lines. Mol Brain Res 32:342–347

    PubMed  CAS  Google Scholar 

  • Williams JP, Thompson JP, Rowbotham DJ, Lambert DG (2008a) Human peripheral blood mononuclear cells produce pre-pro-nociceptin/orphanin FQ mRNA. Anesth Analg 106:865–866

    PubMed  CAS  Google Scholar 

  • Williams JP, Thompson JP, Young SP, Gold SJ, McDonald J, Rowbotham DJ, Lambert DG (2008b) Nociceptin and urotensin-II concentrations in critically ill patients with sepsis. Br J Anaesth 100:810–814

    PubMed  CAS  Google Scholar 

  • Witta J, Buzas B, Cox BM (2003) Traumatic brain injury induces nociceptin/orphanin FQ expression in neurons of the rat cerebral cortex. J Neurotrauma 20:523–532

    PubMed  Google Scholar 

  • Zhang N, Inan S, Cowan A, Sun R, Wang JM, Rogers TJ, Caterina M, Oppenheim JJ (2005) A proinflammatory chemokine, CCL3, sensitizes the heat-and capsaicin-gated ion channel TRPV1. Proc Natl Acad Sci 102:4536–4541

    PubMed  CAS  Google Scholar 

  • Zhang Y, Gandhi PR, Standifer KM (2012) Increased nociceptive sensitivity and nociceptin/orphanin FQ levels in a rat model of PTSD. Mol Pain 8:76

    PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang L, Stuber F, Stamer UM (2013) Inflammatory mediators influence the expression of nociceptin and its receptor in human whole blood cultures. PLoS One 8:e74138

    PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang L, Stuber F, Lippuner C, Schiff M, Stamer UM (2016) Phorbol-12-myristate-13-acetate induces nociceptin in human Mono Mac 6 cells via multiple transduction signalling pathways. Br J Anaesth 117:250–257

    PubMed  CAS  Google Scholar 

  • Zhao H, Huang HW, Wu GC, Cao XD (2002) Effect of orphanin FQ on interleukin-1beta mRNA transcripts in the rat CNS. Neuroscience 114:1019–1031

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Sciences, Anaesthesia Critical Care and Pain Management, University of Leicester, Leicester Royal Infirmary, Leicester, UK

    Salim Kadhim, Mark F. Bird & David G. Lambert

Authors
  1. Salim Kadhim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark F. Bird
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David G. Lambert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David G. Lambert .

Editor information

Editors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Winston-Salem, NC, USA

    Mei-Chuan Ko

  2. Department of Medical Sciences, Section of Pharmacology, University of Ferrara, Ferrara, Italy

    Girolamo Caló

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kadhim, S., Bird, M.F., Lambert, D.G. (2019). N/OFQ-NOP System in Peripheral and Central Immunomodulation. In: Ko, MC., Caló, G. (eds) The Nociceptin/Orphanin FQ Peptide Receptor. Handbook of Experimental Pharmacology, vol 254. Springer, Cham. https://doi.org/10.1007/164_2018_203

Download citation

Publish with us

Policies and ethics

Search

Navigation