Advertisement

pp 1-15 | Cite as

N/OFQ-NOP System in Peripheral and Central Immunomodulation

  • Salim Kadhim
  • Mark F. Bird
  • David G. LambertEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series

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.

Keywords

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

Notes

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.

References

  1. Acosta C, Davies A (2008) Bacterial lipopolysaccharide regulates nociceptin expression in sensory neurons. J Neurosci Res 86:1077–1086Google Scholar
  2. Al-Hashimi M, Scott SW, Thompson JP, Lambert DG (2013) Opioids and immune modulation: more questions than answers. Br J Anaesth 111:80–88Google Scholar
  3. 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 116:423–429Google Scholar
  4. 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 683:285–293Google Scholar
  5. Araque A, Navarrete M (2010) Glial cells in neuronal network function. Philos Trans R Soc Lond B Biol Sci 365:2375–2381Google Scholar
  6. Arjomand J, Cole S, Evans CJ (2002) Novel orphanin FQ/nociceptin transcripts are expressed in human immune cells. J Neuroimmunol 130:100–108Google Scholar
  7. Attwell D, Buchan AM, Charpak S, Lauritzen M, MacVicar BA, Newman EA (2010) Glial and neuronal control of brain blood flow. Nature 468:232–243Google Scholar
  8. Bailey MS, Shipley MT (1993) Astrocyte subtypes in the rat olfactory bulb: morphological heterogeneity and differential laminar distribution. J Comp Neurol 328:501–526Google Scholar
  9. Bakiri Y, Burzomato V, Frugier G, Hamilton NB, Karadottir R, Attwell D (2009) Glutamatergic signaling in the brain’s white matter. Neuroscience 158:266–274Google Scholar
  10. 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 26:1492–1496Google Scholar
  11. Basu S, Dasgupta PS (2000) Dopamine, a neurotransmitter, influences the immune system. J Neuroimmunol 102:113–124Google Scholar
  12. 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 140:89–104Google Scholar
  13. Beggs S, Salter MW (2006) Neuropathic pain: symptoms, models, and mechanisms. Drug Dev Res 67:289–301Google Scholar
  14. Bidlack JM (2000) Detection and function of opioid receptors on cells from the immune system. Clin Diagn Lab Immunol 7:719Google Scholar
  15. 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 175:4496Google Scholar
  16. Boddeke EWGM (2001) Involvement of chemokines in pain. Eur J Pharmacol 429:115–119Google Scholar
  17. Bundgaard M, Abbott NJ (2008) All vertebrates started out with a glial blood-brain barrier 4–500 million years ago. Glia 56:699–708Google Scholar
  18. Buzas B (2002) Regulation of nociceptin/orphanin FQ gene expression in astrocytes by ceramide. Neuroreport 13:1707–1710Google Scholar
  19. 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 71:556–563Google Scholar
  20. 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 7:1123–1128Google Scholar
  21. 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 40:153–158Google Scholar
  22. Carare RO, Hawkes CA, Weller RO (2014) Afferent and efferent immunological pathways of the brain. Anatomy, function and failure. Brain Behav Immun 36:9–14Google Scholar
  23. 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 34:2284–2290Google Scholar
  24. Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354:610–621Google Scholar
  25. Colton CA, Wilcock DM (2010) Assessing activation states in microglia. CNS Neurol Disord Drug Targets 9:174–191Google Scholar
  26. Cornell-Bell AH, Finkbeiner SM, Cooper MS, Smith SJ (1990) Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247:470–473Google Scholar
  27. 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 49:312–319Google Scholar
  28. Davoust N, Vuaillat C, Androdias G, Nataf S (2008) From bone marrow to microglia: barriers and avenues. Trends Immunol 29:227–234Google Scholar
  29. Devine DP, Watson SJ, Akil H (2001) Nociceptin/orphanin FQ regulates neuroendocrine function of the limbic–hypothalamic–pituitary–adrenal axis. Neuroscience 102:541–553Google Scholar
  30. Eriksson KS, Stevens DR, Haas HL (2000) Opposite modulation of histaminergic neurons by nociceptin and morphine. Neuropharmacology 39:2492–2498Google Scholar
  31. 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 60:125–136Google Scholar
  32. Finley MJ, Happel CM, Kaminsky DE, Rogers TJ (2008) Opioid and nociceptin receptors regulate cytokine and cytokine receptor expression. Cell Immunol 252:146–154Google Scholar
  33. Fiset ME, Gilbert C, Poubelle PE, Pouliot M (2003) Human neutrophils as a source of nociceptin: a novel link between pain and inflammation. Biochemistry 42:10498–10505Google Scholar
  34. 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 144:275–285Google Scholar
  35. Galea I, Bechmann I, Perry VH (2007) What is immune privilege (not)? Trends Immunol 28:12–18Google Scholar
  36. Giaume C, Kirchhoff F, Matute C, Reichenbach A, Verkhratsky A (2007) Glia: the fulcrum of brain diseases. Cell Death Differ 14:1324–1335Google Scholar
  37. 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 26:431–437Google Scholar
  38. 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 13:138–145Google Scholar
  39. 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 178:218–224Google Scholar
  40. Hanisch U-K, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394Google Scholar
  41. Herz J, Filiano AJ, Smith A, Yogev N, Kipnis J (2017) Myeloid cells in the central nervous system. Immunity 46:943–956Google Scholar
  42. 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 34:187–191Google Scholar
  43. Hussey HH, Katz S (1950) Infections resulting from narcotic addiction: report of 102 cases. Am J Med 9:186–193Google Scholar
  44. 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 32:11187–11200Google Scholar
  45. Inoue K, Tsuda M (2018) Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential. Nat Rev Neurosci 19:138Google Scholar
  46. Ji R-R, Suter MR (2007) p38 MAPK, microglial signaling, and neuropathic pain. Mol Pain 3:33Google Scholar
  47. 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 128:2675–2688Google Scholar
  48. Kadhim S, McDonald J, Lambert D (2018a) Nociceptin/Orphanin FQ (NOP) receptor is differentially expressed on glial cells. Br J Anaesth 120:e6Google Scholar
  49. Kadhim S, McDonald J, Lambert DG (2018b) Opioids, gliosis and central immunomodulation. J Anesth 32:756–767Google Scholar
  50. 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 39:1081–1092Google Scholar
  51. 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 79:93–98Google Scholar
  52. 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 161:21–28Google Scholar
  53. Kettenmann H, Verkhratsky A (2008) Neuroglia: the 150 years after. Trends Neurosci 31:653–659Google Scholar
  54. 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 41:1096–1102Google Scholar
  55. 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 81:955–963Google Scholar
  56. Lambert DG (2008) The nociceptin/orphanin FQ receptor: a target with broad therapeutic potential. Nat Rev Drug Discov 7:694–710Google Scholar
  57. 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 115:71–83Google Scholar
  58. 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 127:355–360Google Scholar
  59. 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 62:131–139Google Scholar
  60. Magistretti PJ (2006) Neuron–glia metabolic coupling and plasticity. J Exp Biol 209:2304–2311Google Scholar
  61. 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 44:43–48Google Scholar
  62. Marchand F, Perretti M, McMahon SB (2005) Role of the immune system in chronic pain. Nat Rev Neurosci 6:521–532Google Scholar
  63. 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 24:6659–6666Google Scholar
  64. 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 25:9591–9601Google Scholar
  65. Mattson MP, Chan SL (2003) Neuronal and glial calcium signaling in Alzheimer’s disease. Cell Calcium 34:385–397Google Scholar
  66. Meis S, Pape HC (2001) Control of glutamate and GABA release by nociceptin/orphanin FQ in the rat lateral amygdala. J Physiol 532:701–712Google Scholar
  67. 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 65:2003–2023Google Scholar
  68. 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 311:17–20Google Scholar
  69. 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 65:21–30Google Scholar
  70. Mulligan SJ, MacVicar BA (2004) Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature 431:195–199Google Scholar
  71. Murphy NP, Maidment NT (1999) Orphanin FQ/nociceptin modulation of mesolimbic dopamine transmission determined by microdialysis. J Neurochem 73:179–186Google Scholar
  72. Murphy NP, Ly HT, Maidment NT (1996) Intracerebroventricular orphanin FQ/nociceptin suppresses dopamine release in the nucleus accumbens of anaesthetized rats. Neuroscience 75:1–4Google Scholar
  73. 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 32:1–6Google Scholar
  74. Nedergaard M, Ransom B, Goldman SA (2003) New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci 26:523–530Google Scholar
  75. 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 119:1081–1083Google Scholar
  76. 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 21:5027–5035Google Scholar
  77. 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 81:184–192Google Scholar
  78. Pettersson LM, Sundler F, Danielsen N (2002) Expression of orphanin FQ/nociceptin and its receptor in rat peripheral ganglia and spinal cord. Brain Res 945:266–275Google Scholar
  79. 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 2014:762930Google Scholar
  80. Powell EM, Geller HM (1999) Dissection of astrocyte-mediated cues in neuronal guidance and process extension. Glia 26:73–83Google Scholar
  81. 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 3:1289–1300Google Scholar
  82. 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 306:624–630Google Scholar
  83. 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 9:72Google Scholar
  84. Raper D, Louveau A, Kipnis J (2016) How do meningeal lymphatic vessels drain the CNS? Trends Neurosci 39:581–586Google Scholar
  85. Scholz J, Woolf CJ (2007) The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 10:1361Google Scholar
  86. Seifert G, Schilling K, Steinhäuser C (2006) Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat Rev Neurosci 7:194Google Scholar
  87. 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 166:3650–3654Google Scholar
  88. Shah S, Page CP, Spina D (1998) Nociceptin inhibits non-adrenergic non-cholinergic contraction in guinea-pig airway. Br J Pharmacol 125:510–516Google Scholar
  89. 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:P587Google Scholar
  90. 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 173:1286–1301Google Scholar
  91. Smith K (2010) Neuroscience: settling the great glia debate. Nature 468:160–162Google Scholar
  92. 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 106:566–572Google Scholar
  93. 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 45:397–407Google Scholar
  94. Thomas R, Stover C, Lambert DG, Thompson JP (2014) Nociceptin system as a target in sepsis? J Anesth 28:759–767Google Scholar
  95. 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:e76682Google Scholar
  96. 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 26:1497–1502Google Scholar
  97. Tsao C-W, Lin Y-S, Cheng J-T (1997) Effect of dopamine on immune cell proliferation in mice. Life Sci 61:PL361–PL371Google Scholar
  98. Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6:626Google Scholar
  99. Watkins LR, Maier SF (2000) The pain of being sick: implications of immune-to-brain communication for understanding pain. Annu Rev Psychol 51:29–57Google Scholar
  100. Watkins LR, Milligan ED, Maier SF (2001) Glial activation: a driving force for pathological pain. Trends Neurosci 24:450–455Google Scholar
  101. 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 32:342–347Google Scholar
  102. Williams JP, Thompson JP, Rowbotham DJ, Lambert DG (2008a) Human peripheral blood mononuclear cells produce pre-pro-nociceptin/orphanin FQ mRNA. Anesth Analg 106:865–866Google Scholar
  103. 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 100:810–814Google Scholar
  104. Witta J, Buzas B, Cox BM (2003) Traumatic brain injury induces nociceptin/orphanin FQ expression in neurons of the rat cerebral cortex. J Neurotrauma 20:523–532Google Scholar
  105. 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 102:4536–4541Google Scholar
  106. Zhang Y, Gandhi PR, Standifer KM (2012) Increased nociceptive sensitivity and nociceptin/orphanin FQ levels in a rat model of PTSD. Mol Pain 8:76Google Scholar
  107. 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:e74138Google Scholar
  108. 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 117:250–257Google Scholar
  109. Zhao H, Huang HW, Wu GC, Cao XD (2002) Effect of orphanin FQ on interleukin-1beta mRNA transcripts in the rat CNS. Neuroscience 114:1019–1031Google Scholar

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

Personalised recommendations