Advertisement

Electrophysiological Actions of N/OFQ

  • Bryony L. WintersEmail author
  • Macdonald J. Christie
  • Christopher W. Vaughan
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 254)

Abstract

Whilst the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) has similar intracellular coupling mechanisms to opioid receptors, it has distinct modulatory effects on physiological functions such as pain. These actions range from agonistic to antagonistic interactions with classical opioids within the spinal cord and brain, respectively. Understanding the electrophysiological actions of N/OFQ has been crucial in ascertaining the mechanisms by which these agonistic and antagonistic interactions occur. These similarities and differences between N/OFQ and opioids are due to the relative location of NOP versus opioid receptors on specific neuronal elements within these CNS regions. These mechanisms result in varied cellular actions including postsynaptic modulation of ion channels and presynaptic regulation of neurotransmitter release.

Keywords

Electrophysiology G-protein coupled receptors Nociceptin/orphanin FQ Opioids Pain 

References

  1. Abdulla FA, Smith PA (1997) Nociceptin inhibits t-type ca2+ channel current in rat sensory neurons by a g-protein-independent mechanism. J Neurosci 17:8721–8728CrossRefGoogle Scholar
  2. Abdulla FA, Smith PA (1998) Axotomy reduces the effect of analgesic opioids yet increases the effect of nociceptin on dorsal root ganglion neurons. J Neurosci 18:9685–9694CrossRefGoogle Scholar
  3. Ahmadi S, Kotalla C, Guhring H, Takeshima H, Pahl A, Zeilhofer HU (2001a) Modulation of synaptic transmission by nociceptin/orphanin fq and nocistatin in the spinal cord dorsal horn of mutant mice lacking the nociceptin/orphanin fq receptor. Mol Pharmacol 59:612–618PubMedGoogle Scholar
  4. Ahmadi S, Liebel JT, Zeilhofer HU (2001b) The role of the orl1 receptor in the modulation of spinal neurotransmission by nociceptin/orphanin fq and nocistatin. Eur J Pharmacol 412:39–44PubMedGoogle Scholar
  5. Alder J, Kallman S, Palmieri A, Khadim F, Ayer JJ, Kumar S, Tsung K, Grinberg I, Thakker-Varia S (2013) Neuropeptide orphanin fq inhibits dendritic morphogenesis through activation of rhoa. Dev Neurobiol 73:769–784PubMedGoogle Scholar
  6. Altier C, Khosravani H, Evans RM, Hameed S, Peloquin JB, Vartian BA, Chen L, Beedle AM, Ferguson SS, Mezghrani A, Dubel SJ, Bourinet E, McRory JE, Zamponi GW (2006) Orl1 receptor-mediated internalization of n-type calcium channels. Nat Neurosci 9:31–40PubMedGoogle Scholar
  7. Andrade A, Denome S, Jiang YQ, Marangoudakis S, Lipscombe D (2010) Opioid inhibition of n-type ca2+ channels and spinal analgesia couple to alternative splicing. Nat Neurosci 13:1249–1256PubMedPubMedCentralGoogle Scholar
  8. Anton B, Fein J, To T, Li X, Silberstein L, Evans CJ (1996) Immunohistochemical localization of orl-1 in the central nervous system of the rat. J Comp Neurol 368:229–251PubMedGoogle Scholar
  9. Arvidsson U, Dado RJ, Riedl M, Lee JH, Law PY, Loh HH, Elde R, Wessendorf MW (1995) Delta-opioid receptor immunoreactivity: distribution in brainstem and spinal cord, and relationship to biogenic amines and enkephalin. J Neurosci 15:1215–1235PubMedGoogle Scholar
  10. Bantikyan A, Song G, Feinberg-Zadek P, Poon CS (2009) Intrinsic and synaptic long-term depression of nts relay of nociceptin- and capsaicin-sensitive cardiopulmonary afferents hyperactivity. Pflugers Arch 457:1147–1159PubMedGoogle Scholar
  11. Basbaum AI, Fields HL (1984) Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 7:309–338PubMedGoogle Scholar
  12. Basbaum AI, Bautista DM, Scherrer G, Julius D (2009) Cellular and molecular mechanisms of pain. Cell 139:267–284PubMedPubMedCentralGoogle Scholar
  13. Beedle AM, McRory JE, Poirot O, Doering CJ, Altier C, Barrere C, Hamid J, Nargeot J, Bourinet E, Zamponi GW (2004) Agonist-independent modulation of n-type calcium channels by orl1 receptors. Nat Neurosci 7:118–125PubMedGoogle Scholar
  14. Behbehani MM, Jiang M, Chandler SD (1990) The effect of [met]enkephalin on the periaqueductal gray neurons of the rat: an in vitro study. Neuroscience 38:373–380PubMedGoogle Scholar
  15. Bell TJ, Thaler C, Castiglioni AJ, Helton TD, Lipscombe D (2004) Cell-specific alternative splicing increases calcium channel current density in the pain pathway. Neuron 41:127–138PubMedGoogle Scholar
  16. Blackmer T, Larsen EC, Bartleson C, Kowalchyk JA, Yoon EJ, Preininger AM, Alford S, Hamm HE, Martin TF (2005) G protein betagamma directly regulates snare protein fusion machinery for secretory granule exocytosis. Nat Neurosci 8:421–425PubMedGoogle Scholar
  17. Blaesse P, Goedecke L, Bazelot M, Capogna M, Pape HC, Jungling K (2015) Mu-opioid receptor-mediated inhibition of intercalated neurons and effect on synaptic transmission to the central amygdala. J Neurosci 35:7317–7325PubMedPubMedCentralGoogle Scholar
  18. Blanchet C, Luscher C (2002) Desensitization of mu-opioid receptor-evoked potassium currents: initiation at the receptor, expression at the effector. Proc Natl Acad Sci U S A 99:4674–4679PubMedPubMedCentralGoogle Scholar
  19. Bongsebandhu-phubhakdi S, Manabe T (2007) The neuropeptide nociceptin is a synaptically released endogenous inhibitor of hippocampal long-term potentiation. J Neurosci 27:4850–4858PubMedGoogle Scholar
  20. Borgland SL, Connor M, Christie MJ (2001) Nociceptin inhibits calcium channel currents in a subpopulation of small nociceptive trigeminal ganglion neurons in mouse. J Physiol 536:35–47PubMedGoogle Scholar
  21. Brailoiu GC, Lai CC, Chen CT, Hwang LL, Lin HH, Dun NJ (2002) Sympathoinhibitory action of nociceptin in the rat spinal cord. Clin Exp Pharmacol Physiol 29:233–237PubMedGoogle Scholar
  22. Calo G, Rizzi A, Marzola G, Guerrini R, Salvadori S, Beani L, Regoli D, Bianchi C (1998) Pharmacological characterization of the nociceptin receptor mediating hyperalgesia in the mouse tail withdrawal assay. Br J Pharmacol 125:373–378PubMedGoogle Scholar
  23. Campion KN, Saville KA, Morgan MM (2016) Relative contribution of the dorsal raphe nucleus and ventrolateral periaqueductal gray to morphine antinociception and tolerance in the rat. Eur J Neurosci 44:2667–2672PubMedGoogle Scholar
  24. Castiglioni AJ, Raingo J, Lipscombe D (2006) Alternative splicing in the c-terminus of cav2.2 controls expression and gating of n-type calcium channels. J Physiol 576:119–134PubMedGoogle Scholar
  25. Chan JS, Yung LY, Lee JW, Wu YL, Pei G, Wong YH (1998) Pertussis toxin-insensitive signaling of the orl1 receptor: coupling to gz and g16 proteins. J Neurochem 71:2203–2210PubMedGoogle Scholar
  26. Chee MJ, Price CJ, Statnick MA, Colmers WF (2011) Nociceptin/orphanin fq suppresses the excitability of neurons in the ventromedial nucleus of the hypothalamus. J Physiol 589:3103–3114PubMedGoogle Scholar
  27. Chen YL, Li AH, Yeh TH, Chou AH, Wang HL (2009) Nocistatin and nociceptin exert opposite effects on the excitability of central amygdala nucleus-periaqueductal gray projection neurons. Mol Cell Neurosci 40:76–88PubMedGoogle Scholar
  28. Cheng PY, Liu-Chen LY, Pickel VM (1997) Dual ultrastructural immunocytochemical labeling of mu and delta opioid receptors in the superficial layers of the rat cervical spinal cord. Brain Res 778:367–380PubMedGoogle Scholar
  29. Cheong E, Shin HS (2013) T-type ca2+ channels in normal and abnormal brain functions. Physiol Rev 93:961–992PubMedGoogle Scholar
  30. Chieng B, Christie MJ (1994a) Hyperpolarization by opioids acting on mu-receptors of a sub-population of rat periaqueductal gray neurones in vitro. Br J Pharmacol 113:121–128PubMedGoogle Scholar
  31. Chieng B, Christie MJ (1994b) Inhibition by opioids acting on mu-receptors of gabaergic and glutamatergic postsynaptic potentials in single rat periaqueductal gray neurones in vitro. Br J Pharmacol 113:303–309PubMedGoogle Scholar
  32. Chieng B, Christie MJ (1995) Hyperpolarization by gabab receptor agonists in mid-brain periaqueductal gray neurones in vitro. Br J Pharmacol 116:1583–1588PubMedGoogle Scholar
  33. Chieng B, Christie MJ (2009) Chronic morphine treatment induces functional delta-opioid receptors in amygdala neurons that project to periaqueductal grey. Neuropharmacology 57:430–437PubMedGoogle Scholar
  34. Chieng B, Christie MJ (2010) Somatostatin and nociceptin inhibit neurons in the central nucleus of amygdala that project to the periaqueductal grey. Neuropharmacology 59:425–430PubMedGoogle Scholar
  35. Chieng BC, Christie MJ, Osborne PB (2006) Characterization of neurons in the rat central nucleus of the amygdala: cellular physiology, morphology, and opioid sensitivity. J Comp Neurol 497:910–927PubMedGoogle Scholar
  36. Chin JH, Harris K, MacTavish D, Jhamandas JH (2002) Nociceptin/orphanin fq modulation of ionic conductances in rat basal forebrain neurons. J Pharmacol Exp Ther 303:188–195PubMedGoogle Scholar
  37. Chiou LC (2001) Differential antagonism by naloxone benzoylhydrazone of the activation of inward rectifying k+ channels by nociceptin and a mu-opioid in rat periaqueductal grey slices. Naunyn Schmiedebergs Arch Pharmacol 363:583–589PubMedGoogle Scholar
  38. Chiou LC, Chuang KC, Wichmann J, Adam G (2004) Ro 64-6198 [(1s,3as)-8-(2,3,3a,4,5,6-hexahydro-1h-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro [4.5]decan-4-one] acts differently from nociceptin/orphanin fq in rat periaqueductal gray slices. J Pharmacol Exp Ther 311:645–651PubMedGoogle Scholar
  39. Cho YW, Han SH, Min BI, Rhee JS, Akaike N (2001) Antagonizing effect of protein kinase c activation on the mu-opioid agonist-induced inhibition of high voltage-activated calcium current in rat periaqueductal gray neuron. Brain Res 916:61–69PubMedGoogle Scholar
  40. Christie MJ, Williams JT, Osborne PB, Bellchambers CE (1997) Where is the locus in opioid withdrawal? Trends Pharmacol Sci 18:134–140PubMedGoogle Scholar
  41. Cleary DR, Neubert MJ, Heinricher MM (2008) Are opioid-sensitive neurons in the rostral ventromedial medulla inhibitory interneurons? Neuroscience 151:564–571PubMedGoogle Scholar
  42. Connor M, Christie MJ (1998) Modulation of ca2+ channel currents of acutely dissociated rat periaqueductal grey neurons. J Physiol 509(Pt 1):47–58PubMedGoogle Scholar
  43. Connor M, Christie MD (1999) Opioid receptor signalling mechanisms. Clin Exp Pharmacol Physiol 26:493–499PubMedGoogle Scholar
  44. Connor M, Vaughan CW, Chieng B, Christie MJ (1996a) Nociceptin receptor coupling to a potassium conductance in rat locus coeruleus neurones in vitro. Br J Pharmacol 119:1614–1618PubMedPubMedCentralGoogle Scholar
  45. Connor M, Yeo A, Henderson G (1996b) The effect of nociceptin on ca2+ channel current and intracellular ca2+ in the sh-sy5y human neuroblastoma cell line. Br J Pharmacol 118:205–207PubMedGoogle Scholar
  46. Connor M, Vaughan CW, Jennings EA, Allen RG, Christie MJ (1999) Nociceptin, phe(1)psi-nociceptin(1-13), nocistatin and prepronociceptin(154-181) effects on calcium channel currents and a potassium current in rat locus coeruleus in vitro. Br J Pharmacol 128:1779–1787PubMedGoogle Scholar
  47. Dang VC, Napier IA, Christie MJ (2009) Two distinct mechanisms mediate acute mu-opioid receptor desensitization in native neurons. J Neurosci 29:3322–3327PubMedGoogle Scholar
  48. Dang VC, Chieng BC, Christie MJ (2012) Prolonged stimulation of mu-opioid receptors produces beta-arrestin-2-mediated heterologous desensitization of alpha(2)-adrenoceptor function in locus ceruleus neurons. Mol Pharmacol 82:473–480PubMedGoogle Scholar
  49. Donica CL, Awwad HO, Thakker DR, Standifer KM (2013) Cellular mechanisms of nociceptin/orphanin fq (n/ofq) peptide (nop) receptor regulation and heterologous regulation by n/ofq. Mol Pharmacol 83:907–918PubMedGoogle Scholar
  50. Duvarci S, Pare D (2014) Amygdala microcircuits controlling learned fear. Neuron 82:966–980PubMedPubMedCentralGoogle Scholar
  51. Eckert WA 3rd, Willcockson HH, Light AR (2001) Interference of biocytin with opioid-evoked hyperpolarization and membrane properties of rat spinal substantia gelatinosa neurons. Neurosci Lett 297:117–120PubMedGoogle Scholar
  52. Eckert WA 3rd, McNaughton KK, Light AR (2003) Morphology and axonal arborization of rat spinal inner lamina ii neurons hyperpolarized by mu-opioid-selective agonists. J Comp Neurol 458:240–256PubMedGoogle Scholar
  53. Emmerson PJ, Miller RJ (1999) Pre- and postsynaptic actions of opioid and orphan opioid agonists in the rat arcuate nucleus and ventromedial hypothalamus in vitro. J Physiol 517(Pt 2):431–445PubMedPubMedCentralGoogle Scholar
  54. Endoh T (2006) Pharmacological characterization of inhibitory effects of postsynaptic opioid and cannabinoid receptors on calcium currents in neonatal rat nucleus tractus solitarius. Br J Pharmacol 147:391–401PubMedPubMedCentralGoogle Scholar
  55. Evans RM, You H, Hameed S, Altier C, Mezghrani A, Bourinet E, Zamponi GW (2010) Heterodimerization of orl1 and opioid receptors and its consequences for n-type calcium channel regulation. J Biol Chem 285:1032–1040PubMedGoogle Scholar
  56. Faber ES, Chambers JP, Evans RH, Henderson G (1996) Depression of glutamatergic transmission by nociceptin in the neonatal rat hemisected spinal cord preparation in vitro. Br J Pharmacol 119:189–190PubMedPubMedCentralGoogle Scholar
  57. Fernandez-Alacid L, Watanabe M, Molnar E, Wickman K, Lujan R (2011) Developmental regulation of g protein-gated inwardly-rectifying k+ (girk/kir3) channel subunits in the brain. Eur J Neurosci 34:1724–1736PubMedPubMedCentralGoogle Scholar
  58. Fields HL, Bry J, Hentall I, Zorman G (1983a) The activity of neurons in the rostral medulla of the rat during withdrawal from noxious heat. J Neurosci 3:2545–2552PubMedGoogle Scholar
  59. Fields HL, Vanegas H, Hentall ID, Zorman G (1983b) Evidence that disinhibition of brain stem neurones contributes to morphine analgesia. Nature 306:684–686PubMedGoogle Scholar
  60. Finnegan TF, Chen SR, Pan HL (2006) Mu opioid receptor activation inhibits gabaergic inputs to basolateral amygdala neurons through kv1.1/1.2 channels. J Neurophysiol 95:2032–2041PubMedGoogle Scholar
  61. Ge ZJ, Li C, Zhang LC, Zeng YM, Cao JL, Dai TJ, Wang JK, Cui GX, Tan YF, Zhao YP, Liu GJ (2007) Involvement of local orphanin fq in the development of analgesic tolerance induced by morphine microinjections into the dorsal raphe nucleus of rats. Neurosci Lett 413:233–237PubMedGoogle Scholar
  62. Gerachshenko T, Blackmer T, Yoon EJ, Bartleson C, Hamm HE, Alford S (2005) Gbetagamma acts at the c terminus of snap-25 to mediate presynaptic inhibition. Nat Neurosci 8:597–605PubMedGoogle Scholar
  63. Gompf HS, Moldavan MG, Irwin RP, Allen CN (2005) Nociceptin/orphanin fq (n/ofq) inhibits excitatory and inhibitory synaptic signaling in the suprachiasmatic nucleus (scn). Neuroscience 132:955–965PubMedGoogle Scholar
  64. Grudt TJ, Williams JT (1994) Mu-opioid agonists inhibit spinal trigeminal substantia gelatinosa neurons in guinea pig and rat. J Neurosci 14:1646–1654PubMedGoogle Scholar
  65. Gunther T, Dasgupta P, Mann A, Miess E, Kliewer A, Fritzwanker S, Steinborn R, Schulz S (2018) Targeting multiple opioid receptors- improved analgesics with reduced side effects? Br J Pharmacol 175:2857–2868Google Scholar
  66. Hell JW, Westenbroek RE, Warner C, Ahlijanian MK, Prystay W, Gilbert MM, Snutch TP, Catterall WA (1993) Identification and differential subcellular localization of the neuronal class c and class d l-type calcium channel alpha 1 subunits. J Cell Biol 123:949–962PubMedGoogle Scholar
  67. Hermosilla T, Encina M, Morales D, Moreno C, Conejeros C, Alfaro-Valdes HM, Lagos-Meza F, Simon F, Altier C, Varela D (2017) Prolonged at1r activation induces cav1.2 channel internalization in rat cardiomyocytes. Sci Rep 7:10131PubMedPubMedCentralGoogle Scholar
  68. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y (2010) Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 90:291–366PubMedGoogle Scholar
  69. Hickey L, Li Y, Fyson SJ, Watson TC, Perrins R, Hewinson J, Teschemacher AG, Furue H, Lumb BM, Pickering AE (2014) Optoactivation of locus ceruleus neurons evokes bidirectional changes in thermal nociception in rats. J Neurosci 34:4148–4160PubMedPubMedCentralGoogle Scholar
  70. Hirschberg S, Li Y, Randall A, Kremer EJ, Pickering AE (2017) Functional dichotomy in spinal- vs prefrontal-projecting locus coeruleus modules splits descending noradrenergic analgesia from ascending aversion and anxiety in rats. Elife 6:e29808PubMedPubMedCentralGoogle Scholar
  71. Howorth PW, Teschemacher AG, Pickering AE (2009) Retrograde adenoviral vector targeting of nociresponsive pontospinal noradrenergic neurons in the rat in vivo. J Comp Neurol 512:141–157PubMedPubMedCentralGoogle Scholar
  72. Ikeda K, Kobayashi K, Kobayashi T, Ichikawa T, Kumanishi T, Kishida H, Yano R, Manabe T (1997) Functional coupling of the nociceptin/orphanin fq receptor with the g-protein-activated k+ (girk) channel. Brain Res Mol Brain Res 45:117–126PubMedGoogle Scholar
  73. Ingram S, Wilding TJ, McCleskey EW, Williams JT (1997) Efficacy and kinetics of opioid action on acutely dissociated neurons. Mol Pharmacol 52:136–143PubMedGoogle Scholar
  74. Jeftinija S (1988) Enkephalins modulate excitatory synaptic transmission in the superficial dorsal horn by acting at mu-opioid receptor sites. Brain Res 460:260–268PubMedGoogle Scholar
  75. Jennings EA (2001) Postsynaptic k+ current induced by nociceptin in medullary dorsal horn neurons. Neuroreport 12:645–648PubMedGoogle Scholar
  76. Jolas T, Aghajanian GK (1997) Opioids suppress spontaneous and nmda-induced inhibitory postsynaptic currents in the dorsal raphe nucleus of the rat in vitro. Brain Res 755:229–245PubMedGoogle Scholar
  77. Jones SL, Gebhart GF (1986) Quantitative characterization of ceruleospinal inhibition of nociceptive transmission in the rat. J Neurophysiol 56:1397–1410PubMedGoogle Scholar
  78. Jongeling AC, Johns ME, Murphy AZ, Hammond DL (2009) Persistent inflammatory pain decreases the antinociceptive effects of the mu opioid receptor agonist damgo in the locus coeruleus of male rats. Neuropharmacology 56:1017–1026PubMedPubMedCentralGoogle Scholar
  79. 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 39:1081–1092PubMedPubMedCentralGoogle Scholar
  80. Karschin C, Dissmann E, Stuhmer W, Karschin A (1996) Irk(1-3) and girk(1-4) inwardly rectifying k+ channel mrnas are differentially expressed in the adult rat brain. J Neurosci 16:3559–3570PubMedGoogle Scholar
  81. Katz B, Miledi R (1968) The role of calcium in neuromuscular facilitation. J Physiol 195:481–492PubMedPubMedCentralGoogle Scholar
  82. Kawahara Y, Hesselink MB, van Scharrenburg G, Westerink BH (2004) Tonic inhibition by orphanin fq/nociceptin of noradrenaline neurotransmission in the amygdala. Eur J Pharmacol 485:197–200PubMedPubMedCentralGoogle Scholar
  83. Kiguchi N, Ding H, Ko MC (2016) Central n/ofq-nop receptor system in pain modulation. Adv Pharmacol 75:217–243PubMedPubMedCentralGoogle Scholar
  84. Kim CJ, Rhee JS, Akaike N (1997) Modulation of high-voltage activated ca2+ channels in the rat periaqueductal gray neurons by mu-type opioid agonist. J Neurophysiol 77:1418–1424PubMedGoogle Scholar
  85. Kisilevsky AE, Mulligan SJ, Altier C, Iftinca MC, Varela D, Tai C, Chen L, Hameed S, Hamid J, Macvicar BA, Zamponi GW (2008) D1 receptors physically interact with n-type calcium channels to regulate channel distribution and dendritic calcium entry. Neuron 58:557–570PubMedGoogle Scholar
  86. Knoflach F, Reinscheid RK, Civelli O, Kemp JA (1996) Modulation of voltage-gated calcium channels by orphanin fq in freshly dissociated hippocampal neurons. J Neurosci 16:6657–6664PubMedGoogle Scholar
  87. Kohno T, Ji RR, Ito N, Allchorne AJ, Befort K, Karchewski LA, Woolf CJ (2005) Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord. Pain 117:77–87PubMedGoogle Scholar
  88. Kuzmin A, Sandin J, Terenius L, Ogren SO (2004) Evidence in locomotion test for the functional heterogeneity of orl-1 receptors. Br J Pharmacol 141:132–140PubMedGoogle Scholar
  89. Lai CC, Wu SY, Dun SL, Dun NJ (1997) Nociceptin-like immunoreactivity in the rat dorsal horn and inhibition of substantia gelatinosa neurons. Neuroscience 81:887–891PubMedGoogle Scholar
  90. Lau BK, Vaughan CW (2014) Descending modulation of pain: the gaba disinhibition hypothesis of analgesia. Curr Opin Neurobiol 29:159–164PubMedGoogle Scholar
  91. Le Pichon CE, Chesler AT (2014) The functional and anatomical dissection of somatosensory subpopulations using mouse genetics. Front Neuroanat 8:21PubMedPubMedCentralGoogle Scholar
  92. Lee JJ, Hahm ET, Min BI, Cho YW (2004) Activation of protein kinase c antagonizes the opioid inhibition of calcium current in rat spinal dorsal horn neurons. Brain Res 1017:108–119PubMedGoogle Scholar
  93. Lei Q, Jones MB, Talley EM, Schrier AD, McIntire WE, Garrison JC, Bayliss DA (2000) Activation and inhibition of g protein-coupled inwardly rectifying potassium (kir3) channels by g protein beta gamma subunits. Proc Natl Acad Sci U S A 97:9771–9776PubMedPubMedCentralGoogle Scholar
  94. Lemos JC, Roth CA, Messinger DI, Gill HK, Phillips PE, Chavkin C (2012) Repeated stress dysregulates kappa-opioid receptor signaling in the dorsal raphe through a p38alpha mapk-dependent mechanism. J Neurosci 32:12325–12336PubMedPubMedCentralGoogle Scholar
  95. Li JN, Sheets PL (2018) The central amygdala to periaqueductal gray pathway comprises intrinsically distinct neurons differentially affected in a model of inflammatory pain. J Physiol 596:6289–6305PubMedGoogle Scholar
  96. Li Y, Tatsui CE, Rhines LD, North RY, Harrison DS, Cassidy RM, Johansson CA, Kosturakis AK, Edwards DD, Zhang H, Dougherty PM (2017) Dorsal root ganglion neurons become hyperexcitable and increase expression of voltage-gated t-type calcium channels (cav3.2) in paclitaxel-induced peripheral neuropathy. Pain 158:417–429PubMedPubMedCentralGoogle Scholar
  97. Liao YY, Teng SF, Lin LC, Kolczewski S, Prinssen EP, Lee LJ, Ho IK, Chiou LC (2011) Functional heterogeneity of nociceptin/orphanin fq receptors revealed by (+)-5a compound and ro 64-6198 in rat periaqueductal grey slices. Int J Neuropsychopharmacol 14:977–989PubMedGoogle Scholar
  98. Liebel JT, Swandulla D, Zeilhofer HU (1997) Modulation of excitatory synaptic transmission by nociceptin in superficial dorsal horn neurones of the neonatal rat spinal cord. Br J Pharmacol 121:425–432PubMedPubMedCentralGoogle Scholar
  99. Liu S, Hu HZ, Ren J, Gao C, Gao N, Lin Z, Xia Y, Wood JD (2001) Pre- and postsynaptic inhibition by nociceptin in guinea pig small intestinal myenteric plexus in vitro. Am J Physiol Gastrointest Liver Physiol 281:G237–G246PubMedGoogle Scholar
  100. Llorca-Torralba M, Borges G, Neto F, Mico JA, Berrocoso E (2016) Noradrenergic locus coeruleus pathways in pain modulation. Neuroscience 338:93–113PubMedGoogle Scholar
  101. Llorente J, Lowe JD, Sanderson HS, Tsisanova E, Kelly E, Henderson G, Bailey CP (2012) Mu-opioid receptor desensitization: homologous or heterologous? Eur J Neurosci 36:3636–3642PubMedGoogle Scholar
  102. Lu N, Han M, Yang ZL, Wang YQ, Wu GC, Zhang YQ (2010) Nociceptin/orphanin fq in pag modulates the release of amino acids, serotonin and norepinephrine in the rostral ventromedial medulla and spinal cord in rats. Pain 148:414–425PubMedGoogle Scholar
  103. Lujan R, Aguado C (2015) Localization and targeting of girk channels in mammalian central neurons. Int Rev Neurobiol 123:161–200PubMedGoogle Scholar
  104. Luo C, Kumamoto E, Furue H, Yoshimura M (2001) Nociceptin-induced outward current in substantia gelatinosa neurones of the adult rat spinal cord. Neuroscience 108:323–330PubMedGoogle Scholar
  105. Luo C, Kumamoto E, Furue H, Chen J, Yoshimura M (2002) Nociceptin inhibits excitatory but not inhibitory transmission to substantia gelatinosa neurones of adult rat spinal cord. Neuroscience 109:349–358PubMedGoogle Scholar
  106. Luscher C, Slesinger PA (2010) Emerging roles for g protein-gated inwardly rectifying potassium (girk) channels in health and disease. Nat Rev Neurosci 11:301–315PubMedGoogle Scholar
  107. Macabuag N, Dolphin AC (2015) Alternative splicing in ca(v)2.2 regulates neuronal trafficking via adaptor protein complex-1 adaptor protein motifs. J Neurosci 35:14636–14652PubMedGoogle Scholar
  108. Madamba SG, Schweitzer P, Siggins GR (1999) Nociceptin augments k(+) currents in hippocampal ca1 neurons by both orl-1 and opiate receptor mechanisms. J Neurophysiol 82:1776–1785PubMedGoogle Scholar
  109. Manabe T, Noda Y, Mamiya T, Katagiri H, Houtani T, Nishi M, Noda T, Takahashi T, Sugimoto T, Nabeshima T, Takeshima H (1998) Facilitation of long-term potentiation and memory in mice lacking nociceptin receptors. Nature 394:577–581PubMedGoogle Scholar
  110. Mansour A, Fox CA, Burke S, Meng F, Thompson RC, Akil H, Watson SJ (1994) Mu, delta, and kappa opioid receptor mrna expression in the rat cns: an in situ hybridization study. J Comp Neurol 350:412–438PubMedGoogle Scholar
  111. Marangoudakis S, Andrade A, Helton TD, Denome S, Castiglioni AJ, Lipscombe D (2012) Differential ubiquitination and proteasome regulation of ca(v)2.2 n-type channel splice isoforms. J Neurosci 32:10365–10369PubMedPubMedCentralGoogle Scholar
  112. Margas W, Sedeek K, Ruiz-Velasco V (2008) Coupling specificity of nop opioid receptors to pertussis-toxin-sensitive galpha proteins in adult rat stellate ganglion neurons using small interference rna. J Neurophysiol 100:1420–1432PubMedPubMedCentralGoogle Scholar
  113. Marker CL, Lujan R, Colon J, Wickman K (2006) Distinct populations of spinal cord lamina ii interneurons expressing g-protein-gated potassium channels. J Neurosci 26:12251–12259PubMedGoogle Scholar
  114. Mathis JP, Ryan-Moro J, Chang A, Hom JS, Scheinberg DA, Pasternak GW (1997) Biochemical evidence for orphanin fq/nociceptin receptor heterogeneity in mouse brain. Biochem Biophys Res Commun 230:462–465Google Scholar
  115. Mathis JP, Goldberg IE, Letchworth SR, Ryan-Moro JP, Pasternak GW (1999) Identification of a high-affinity orphanin fq/nociceptin(1-11) binding site in mouse brain. Synapse 34:181–186PubMedGoogle Scholar
  116. Meis S, Pape HC (1998) Postsynaptic mechanisms underlying responsiveness of amygdaloid neurons to nociceptin/orphanin fq. J Neurosci 18:8133–8144PubMedGoogle Scholar
  117. Meis S, Pape HC (2001) Control of glutamate and gaba release by nociceptin/orphanin fq in the rat lateral amygdala. J Physiol 532:701–712PubMedPubMedCentralGoogle Scholar
  118. Meng ID, Johansen JP, Harasawa I, Fields HL (2005) Kappa opioids inhibit physiologically identified medullary pain modulating neurons and reduce morphine antinociception. J Neurophysiol 93:1138–1144PubMedGoogle Scholar
  119. Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, Butour JL, Guillemot JC, Ferrara P, Monsarrat B et al (1995) Isolation and structure of the endogenous agonist of opioid receptor-like orl1 receptor. Nature 377:532–535Google Scholar
  120. Millan MJ (2002) Descending control of pain. Prog Neurobiol 66:355–474PubMedGoogle Scholar
  121. Mogil JS, Grisel JE, Reinscheid RK, Civelli O, Belknap JK, Grandy DK (1996a) Orphanin fq is a functional anti-opioid peptide. Neuroscience 75:333–337Google Scholar
  122. Mogil JS, Grisel JE, Zhangs G, Belknap JK, Grandy DK (1996b) Functional antagonism of mu-, delta- and kappa-opioid antinociception by orphanin fq. Neurosci Lett 214:131–134PubMedGoogle Scholar
  123. Moises HC, Rusin KI, Macdonald RL (1994) Mu- and kappa-opioid receptors selectively reduce the same transient components of high-threshold calcium current in rat dorsal root ganglion sensory neurons. J Neurosci 14:5903–5916PubMedGoogle Scholar
  124. Morgan MM, Grisel JE, Robbins CS, Grandy DK (1997) Antinociception mediated by the periaqueductal gray is attenuated by orphanin fq. Neuroreport 8:3431–3434PubMedGoogle Scholar
  125. Mouledous L (2018) The nociceptin/orphanin fq system and the regulation of memory. Handb Exp Pharmacol.  https://doi.org/10.1007/164_2018_185 Google Scholar
  126. Murali SS, Napier IA, Rycroft BK, Christie MJ (2012) Opioid-related (orl1) receptors are enriched in a subpopulation of sensory neurons and prolonged activation produces no functional loss of surface n-type calcium channels. J Physiol 590:1655–1667PubMedPubMedCentralGoogle Scholar
  127. Nanou E, Catterall WA (2018) Calcium channels, synaptic plasticity, and neuropsychiatric disease. Neuron 98:466–481PubMedGoogle Scholar
  128. Nazzaro C, Rizzi A, Salvadori S, Guerrini R, Regoli D, Zeilhofer HU, Calo G (2007) Ufp-101 antagonizes the spinal antinociceptive effects of nociceptin/orphanin fq: behavioral and electrophysiological studies in mice. Peptides 28:663–669PubMedGoogle Scholar
  129. Nazzaro C, Barbieri M, Varani K, Beani L, Valentino RJ, Siniscalchi A (2010) Swim stress enhances nociceptin/orphanin fq-induced inhibition of rat dorsal raphe nucleus activity in vivo and in vitro: role of corticotropin releasing factor. Neuropharmacology 58:457–464Google Scholar
  130. Neal CR Jr, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Akil H, Watson SJ Jr (1999) Opioid receptor-like (orl1) receptor distribution in the rat central nervous system: comparison of orl1 receptor mrna expression with (125)i-[(14)tyr]-orphanin fq binding. J Comp Neurol 412:563–605Google Scholar
  131. Neal CR Jr, Akil H, Watson SJ Jr (2001) Expression of orphanin fq and the opioid receptor-like (orl1) receptor in the developing human and rat brain. J Chem Neuroanat 22:219–249PubMedGoogle Scholar
  132. 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 119:1081–1083PubMedPubMedCentralGoogle Scholar
  133. North RA, Williams JT (1985) On the potassium conductance increased by opioids in rat locus coeruleus neurones. J Physiol 364:265–280PubMedPubMedCentralGoogle Scholar
  134. Olianas MC, Dedoni S, Boi M, Onali P (2008) Activation of nociceptin/orphanin fq-nop receptor system inhibits tyrosine hydroxylase phosphorylation, dopamine synthesis, and dopamine d(1) receptor signaling in rat nucleus accumbens and dorsal striatum. J Neurochem 107:544–556PubMedGoogle Scholar
  135. Osborne PB, Vaughan CW, Wilson HI, Christie MJ (1996) Opioid inhibition of rat periaqueductal grey neurones with identified projections to rostral ventromedial medulla in vitro. J Physiol 490(Pt 2):383–389PubMedPubMedCentralGoogle Scholar
  136. Ossipov MH, Morimura K, Porreca F (2014) Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care 8:143–151PubMedPubMedCentralGoogle Scholar
  137. Ozawa A, Brunori G, Mercatelli D, Wu J, Cippitelli A, Zou B, Xie XS, Williams M, Zaveri NT, Low S, Scherrer G, Kieffer BL, Toll L (2015) Knock-in mice with nop-egfp receptors identify receptor cellular and regional localization. J Neurosci 35:11682–11693PubMedPubMedCentralGoogle Scholar
  138. Pan ZZ, Williams JT, Osborne PB (1990) Opioid actions on single nucleus raphe magnus neurons from rat and guinea-pig in vitro. J Physiol 427:519–532PubMedPubMedCentralGoogle Scholar
  139. Pan Z, Hirakawa N, Fields HL (2000) A cellular mechanism for the bidirectional pain-modulating actions of orphanin fq/nociceptin. Neuron 26:515–522PubMedGoogle Scholar
  140. Pan YX, Bolan E, Pasternak GW (2002a) Dimerization of morphine and orphanin fq/nociceptin receptors: generation of a novel opioid receptor subtype. Biochem Biophys Res Commun 297:659–663PubMedGoogle Scholar
  141. Pan YZ, Li DP, Chen SR, Pan HL (2002b) Activation of delta-opioid receptors excites spinally projecting locus coeruleus neurons through inhibition of gabaergic inputs. J Neurophysiol 88:2675–2683PubMedGoogle Scholar
  142. Pape HC, Pare D (2010) Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol Rev 90:419–463PubMedPubMedCentralGoogle Scholar
  143. Parsons MP, Hirasawa M (2011) Girk channel-mediated inhibition of melanin-concentrating hormone neurons by nociceptin/orphanin fq. J Neurophysiol 105:1179–1184PubMedGoogle Scholar
  144. Peluso J, LaForge KS, Matthes HW, Kreek MJ, Kieffer BL, Gaveriaux-Ruff C (1998) Distribution of nociceptin/orphanin fq receptor transcript in human central nervous system and immune cells. J Neuroimmunol 81:184–192PubMedGoogle Scholar
  145. Pennock RL, Dicken MS, Hentges ST (2012) Multiple inhibitory g-protein-coupled receptors resist acute desensitization in the presynaptic but not postsynaptic compartments of neurons. J Neurosci 32:10192–10200PubMedPubMedCentralGoogle Scholar
  146. Pettersson LM, Sundler F, Danielsen N (2002) Expression of orphanin fq/nociceptin and its receptor in rat peripheral ganglia and spinal cord. Brain Res 945:266–275PubMedGoogle Scholar
  147. Poulin JF, Chevalier B, Laforest S, Drolet G (2006) Enkephalinergic afferents of the centromedial amygdala in the rat. J Comp Neurol 496:859–876PubMedGoogle Scholar
  148. Pu L, Bao GB, Ma L, Pei G (1999) Acute desensitization of nociceptin/orphanin fq inhibition of voltage-gated calcium channels in freshly dissociated hippocampal neurons. Eur J Neurosci 11:3610–3616PubMedGoogle Scholar
  149. Qu L, Li Y, Tian H, Wang Z, Cui L, Jin H, Wang W, Yang L (2007) Effects of pkc on inhibition of delayed rectifier potassium currents by n/ofq. Biochem Biophys Res Commun 356:582–586PubMedGoogle Scholar
  150. Raingo J, Castiglioni AJ, Lipscombe D (2007) Alternative splicing controls g protein-dependent inhibition of n-type calcium channels in nociceptors. Nat Neurosci 10:285–292PubMedPubMedCentralGoogle Scholar
  151. Randic M, Cheng G, Kojic L (1995) Kappa-opioid receptor agonists modulate excitatory transmission in substantia gelatinosa neurons of the rat spinal cord. J Neurosci 15:6809–6826PubMedGoogle Scholar
  152. Reinscheid RK, Nothacker HP, Bourson A, Ardati A, Henningsen RA, Bunzow JR, Grandy DK, Langen H, Monsma FJ Jr, Civelli O (1995) Orphanin fq: a neuropeptide that activates an opioidlike g protein-coupled receptor. Science 270:792–794PubMedPubMedCentralGoogle Scholar
  153. Reuveny E, Slesinger PA, Inglese J, Morales JM, Iniguez-Lluhi JA, Lefkowitz RJ, Bourne HR, Jan YN, Jan LY (1994) Activation of the cloned muscarinic potassium channel by g protein beta gamma subunits. Nature 370:143–146PubMedGoogle Scholar
  154. Reyes BA, Chavkin C, van Bockstaele EJ (2009) Subcellular targeting of kappa-opioid receptors in the rat nucleus locus coeruleus. J Comp Neurol 512:419–431PubMedPubMedCentralGoogle Scholar
  155. Ring RH, Alder J, Fennell M, Kouranova E, Black IB, Thakker-Varia S (2006) Transcriptional profiling of brain-derived-neurotrophic factor-induced neuronal plasticity: a novel role for nociceptin in hippocampal neurite outgrowth. J Neurobiol 66:361–377PubMedGoogle Scholar
  156. Rizzi D, Bigoni R, Rizzi A, Jenck F, Wichmann J, Guerrini R, Regoli D, Calo G (2001) Effects of ro 64-6198 in nociceptin/orphanin fq-sensitive isolated tissues. Naunyn Schmiedebergs Arch Pharmacol 363:551–555PubMedGoogle Scholar
  157. Roberto M, Siggins GR (2006) Nociceptin/orphanin fq presynaptically decreases gabaergic transmission and blocks the ethanol-induced increase of gaba release in central amygdala. Proc Natl Acad Sci U S A 103:9715–9720PubMedPubMedCentralGoogle Scholar
  158. Ruscheweyh R, Sandkuhler J (2001) Bidirectional actions of nociceptin/orphanin fq on a delta-fibre-evoked responses in rat superficial spinal dorsal horn in vitro. Neuroscience 107:275–281PubMedGoogle Scholar
  159. Ruscheweyh R, Wilder-Smith O, Drdla R, Liu XG, Sandkuhler J (2011) Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy. Mol Pain 7:20PubMedPubMedCentralGoogle Scholar
  160. Saeed AW, Ribeiro-da-Silva A (2012) Non-peptidergic primary afferents are presynaptic to neurokinin-1 receptor immunoreactive lamina i projection neurons in rat spinal cord. Mol Pain 8:64PubMedPubMedCentralGoogle Scholar
  161. Samoriski GM, Gross RA (2000) Functional compartmentalization of opioid desensitization in primary sensory neurons. J Pharmacol Exp Ther 294:500–509PubMedGoogle Scholar
  162. Santos SF, Melnick IV, Safronov BV (2004) Selective postsynaptic inhibition of tonic-firing neurons in substantia gelatinosa by mu-opioid agonist. Anesthesiology 101:1177–1183PubMedGoogle Scholar
  163. Schneider SP, Eckert WA 3rd, Light AR (1998) Opioid-activated postsynaptic, inward rectifying potassium currents in whole cell recordings in substantia gelatinosa neurons. J Neurophysiol 80:2954–2962PubMedGoogle Scholar
  164. Schroder W, Lambert DG, Ko MC, Koch T (2014) Functional plasticity of the n/ofq-nop receptor system determines analgesic properties of nop receptor agonists. Br J Pharmacol 171:3777–3800PubMedPubMedCentralGoogle Scholar
  165. Schroeder JE, McCleskey EW (1993) Inhibition of ca2+ currents by a mu-opioid in a defined subset of rat sensory neurons. J Neurosci 13:867–873PubMedGoogle Scholar
  166. Shane R, Acosta J, Rossi GC, Bodnar RJ (2003) Reciprocal interactions between the amygdala and ventrolateral periaqueductal gray in mediating of q/n(1-17)-induced analgesia in the rat. Brain Res 980:57–70PubMedGoogle Scholar
  167. Shen KZ, Johnson SW (2002) Presynaptic modulation of synaptic transmission by opioid receptor in rat subthalamic nucleus in vitro. J Physiol 541:219–230PubMedPubMedCentralGoogle Scholar
  168. Shirasaki T, Houtani T, Sugimoto T, Matsuda H (2001) Spontaneous transient outward currents: modulation by nociceptin in murine dentate gyrus granule cells. Brain Res 917:191–205PubMedGoogle Scholar
  169. Smith KM, Boyle KA, Mustapa M, Jobling P, Callister RJ, Hughes DI, Graham BA (2016) Distinct forms of synaptic inhibition and neuromodulation regulate calretinin-positive neuron excitability in the spinal cord dorsal horn. Neuroscience 326:10–21PubMedPubMedCentralGoogle Scholar
  170. Sugita S, North RA (1993) Opioid actions on neurons of rat lateral amygdala in vitro. Brain Res 612:151–155PubMedGoogle Scholar
  171. Sugita S, Tanaka E, North RA (1993) Membrane properties and synaptic potentials of three types of neurone in rat lateral amygdala. J Physiol 460:705–718PubMedPubMedCentralGoogle Scholar
  172. Sulaiman MR, Niklasson M, Tham R, Dutia MB (1999) Modulation of vestibular function by nociceptin/orphanin fq: an in vivo and in vitro study. Brain Res 828:74–82PubMedGoogle Scholar
  173. Taddese A, Nah SY, McCleskey EW (1995) Selective opioid inhibition of small nociceptive neurons. Science 270:1366–1369PubMedGoogle Scholar
  174. Tallent MK, Madamba SG, Siggins GR (2001) Nociceptin reduces epileptiform events in ca3 hippocampus via presynaptic and postsynaptic mechanisms. J Neurosci 21:6940–6948PubMedPubMedCentralGoogle Scholar
  175. Tao R, Auerbach SB (2005) Mu-opioids disinhibit and kappa-opioids inhibit serotonin efflux in the dorsal raphe nucleus. Brain Res 1049:70–79PubMedGoogle Scholar
  176. Taverna FA, Georgiou J, McDonald RJ, Hong NS, Kraev A, Salter MW, Takeshima H, Muller RU, Roder JC (2005) Defective place cell activity in nociceptin receptor knockout mice with elevated nmda receptor-dependent long-term potentiation. J Physiol 565:579–591PubMedPubMedCentralGoogle Scholar
  177. Taylor BK, Westlund KN (2017) The noradrenergic locus coeruleus as a chronic pain generator. J Neurosci Res 95:1336–1346PubMedGoogle Scholar
  178. Thompson JM, Neugebauer V (2018) Cortico-limbic pain mechanisms. Neurosci Lett.  https://doi.org/10.1016/j.neulet.2018.11.037 PubMedGoogle Scholar
  179. Tian JH, Xu W, Fang Y, Mogil JS, Grisel JE, Grandy DK, Han JS (1997) Bidirectional modulatory effect of orphanin fq on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat. Br J Pharmacol 120:676–680PubMedPubMedCentralGoogle Scholar
  180. Todd AJ (2010) Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci 11:823–836PubMedPubMedCentralGoogle Scholar
  181. Toll L, Bruchas MR, Calo G, Cox BM, Zaveri NT (2016) Nociceptin/orphanin fq receptor structure, signaling, ligands, functions, and interactions with opioid systems. Pharmacol Rev 68:419–457PubMedPubMedCentralGoogle Scholar
  182. Torrecilla M, Marker CL, Cintora SC, Stoffel M, Williams JT, Wickman K (2002) G-protein-gated potassium channels containing kir3.2 and kir3.3 subunits mediate the acute inhibitory effects of opioids on locus ceruleus neurons. J Neurosci 22:4328–4334PubMedGoogle Scholar
  183. van Bockstaele EJ, Commons K, Pickel VM (1997) Delta-opioid receptor is present in presynaptic axon terminals in the rat nucleus locus coeruleus: relationships with methionine5-enkephalin. J Comp Neurol 388:575–586PubMedGoogle Scholar
  184. Vaughan CW, Christie MJ (1996) Increase by the orl1 receptor (opioid receptor-like1) ligand, nociceptin, of inwardly rectifying k conductance in dorsal raphe nucleus neurones. Br J Pharmacol 117:1609–1611PubMedPubMedCentralGoogle Scholar
  185. Vaughan CW, Ingram SL, Christie MJ (1997) Actions of the orl1 receptor ligand nociceptin on membrane properties of rat periaqueductal gray neurons in vitro. J Neurosci 17:996–1003PubMedGoogle Scholar
  186. Vaughan CW, Connor M, Jennings EA, Marinelli S, Allen RG, Christie MJ (2001) Actions of nociceptin/orphanin fq and other prepronociceptin products on rat rostral ventromedial medulla neurons in vitro. J Physiol 534:849–859PubMedPubMedCentralGoogle Scholar
  187. Vaughan CW, Bagley EE, Drew GM, Schuller A, Pintar JE, Hack SP, Christie MJ (2003) Cellular actions of opioids on periaqueductal grey neurons from c57b16/j mice and mutant mice lacking mor-1. Br J Pharmacol 139:362–367PubMedPubMedCentralGoogle Scholar
  188. Veinante P, Yalcin I, Barrot M (2013) The amygdala between sensation and affect: a role in pain. J Mol Psychiatry 1:9PubMedPubMedCentralGoogle Scholar
  189. Venkatesan P, Baxi S, Evans C, Neff R, Wang X, Mendelowitz D (2003) Glycinergic inputs to cardiac vagal neurons in the nucleus ambiguus are inhibited by nociceptin and mu-selective opioids. J Neurophysiol 90:1581–1588PubMedGoogle Scholar
  190. Wang QP, Nakai Y (1994) The dorsal raphe: an important nucleus in pain modulation. Brain Res Bull 34:575–585PubMedGoogle Scholar
  191. Wang W, Cui Q, Li Y, Li B, Yang X, Cui L, Jin H, Qu L (2010) The role of erk-1/2 in the n/ofq-induced inhibition of delayed rectifier potassium currents. Biochem Biophys Res Commun 394:1058–1062PubMedGoogle Scholar
  192. Wang D, Tawfik VL, Corder G, Low SA, Francois A, Basbaum AI, Scherrer G (2018) Functional divergence of delta and mu opioid receptor organization in cns pain circuits. Neuron 98:90–108.e5PubMedPubMedCentralGoogle Scholar
  193. Wei WZ, Xie CW (1999) Orphanin fq suppresses nmda receptor-dependent long-term depression and depotentiation in hippocampal dentate gyrus. Learn Mem 6:467–477PubMedPubMedCentralGoogle Scholar
  194. Weissbourd B, Ren J, DeLoach KE, Guenthner CJ, Miyamichi K, Luo L (2014) Presynaptic partners of dorsal raphe serotonergic and gabaergic neurons. Neuron 83:645–662PubMedPubMedCentralGoogle Scholar
  195. Werthwein S, Bauer U, Nakazi M, Kathmann M, Schlicker E (1999) Further characterization of the orl1 receptor-mediated inhibition of noradrenaline release in the mouse brain in vitro. Br J Pharmacol 127:300–308PubMedPubMedCentralGoogle Scholar
  196. West WL, Yeomans DC, Proudfit HK (1993) The function of noradrenergic neurons in mediating antinociception induced by electrical stimulation of the locus coeruleus in two different sources of Sprague-Dawley rats. Brain Res 626:127–135PubMedGoogle Scholar
  197. Westenbroek RE, Sakurai T, Elliott EM, Hell JW, Starr TV, Snutch TP, Catterall WA (1995) Immunochemical identification and subcellular distribution of the alpha 1a subunits of brain calcium channels. J Neurosci 15:6403–6418PubMedGoogle Scholar
  198. Wickman KD, Iniguez-Lluhl JA, Davenport PA, Taussig R, Krapivinsky GB, Linder ME, Gilman AG, Clapham DE (1994) Recombinant g-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel. Nature 368:255–257PubMedGoogle Scholar
  199. Williams SR, Mitchell SJ (2008) Direct measurement of somatic voltage clamp errors in central neurons. Nat Neurosci 11:790–798PubMedGoogle Scholar
  200. Williams JT, Egan TM, North RA (1982) Enkephalin opens potassium channels on mammalian central neurones. Nature 299:74–77PubMedGoogle Scholar
  201. Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S, Koch T, Evans CJ, Christie MJ (2013) Regulation of mu-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Pharmacol Rev 65:223–254PubMedPubMedCentralGoogle Scholar
  202. Winters BL, Gregoriou GC, Kissiwaa SA, Wells OA, Medagoda DI, Hermes SM, Burford NT, Alt A, Aicher SA, Bagley EE (2017) Endogenous opioids regulate moment-to-moment neuronal communication and excitability. Nat Commun 8:14611PubMedPubMedCentralGoogle Scholar
  203. Wu ZZ, Chen SR, Pan HL (2004) Differential sensitivity of n- and p/q-type ca2+ channel currents to a mu opioid in isolectin b4-positive and -negative dorsal root ganglion neurons. J Pharmacol Exp Ther 311:939–947PubMedGoogle Scholar
  204. Xie GX, Meuser T, Pietruck C, Sharma M, Palmer PP (1999) Presence of opioid receptor-like (orl1) receptor mrna splice variants in peripheral sensory and sympathetic neuronal ganglia. Life Sci 64:2029–2037PubMedPubMedCentralGoogle Scholar
  205. Xie X, Wisor JP, Hara J, Crowder TL, LeWinter R, Khroyan TV, Yamanaka A, Diano S, Horvath TL, Sakurai T, Toll L, Kilduff TS (2008) Hypocretin/orexin and nociceptin/orphanin fq coordinately regulate analgesia in a mouse model of stress-induced analgesia. J Clin Invest 118:2471–2481PubMedPubMedCentralGoogle Scholar
  206. Yamada M, Inanobe A, Kurachi Y (1998) G protein regulation of potassium ion channels. Pharmacol Rev 50:723–760PubMedGoogle Scholar
  207. Yu TP, Xie CW (1998) Orphanin fq/nociceptin inhibits synaptic transmission and long-term potentiation in rat dentate gyrus through postsynaptic mechanisms. J Neurophysiol 80:1277–1284PubMedGoogle Scholar
  208. Yu TP, Fein J, Phan T, Evans CJ, Xie CW (1997) Orphanin fq inhibits synaptic transmission and long-term potentiation in rat hippocampus. Hippocampus 7:88–94PubMedGoogle Scholar
  209. Yuan LL, Chen X (2006) Diversity of potassium channels in neuronal dendrites. Prog Neurobiol 78:374–389PubMedGoogle Scholar
  210. Yung LY, Joshi SA, Chan RY, Chan JS, Pei G, Wong YH (1999) Galphal1 (galpha14) couples the opioid receptor-like1 receptor to stimulation of phospholipase c. J Pharmacol Exp Ther 288:232–238PubMedGoogle Scholar
  211. Zamponi GW, Currie KP (2013) Regulation of ca(v)2 calcium channels by g protein coupled receptors. Biochim Biophys Acta 1828:1629–1643PubMedGoogle Scholar
  212. Zamponi GW, Striessnig J, Koschak A, Dolphin AC (2015) The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential. Pharmacol Rev 67:821–870PubMedPubMedCentralGoogle Scholar
  213. Zeilhofer HU, Selbach UM, Guhring H, Erb K, Ahmadi S (2000) Selective suppression of inhibitory synaptic transmission by nocistatin in the rat spinal cord dorsal horn. J Neurosci 20:4922–4929PubMedGoogle Scholar
  214. Zhang NR, Planer W, Siuda ER, Zhao HC, Stickler L, Chang SD, Baird MA, Cao YQ, Bruchas MR (2012) Serine 363 is required for nociceptin/orphanin fq opioid receptor (nopr) desensitization, internalization, and arrestin signaling. J Biol Chem 287:42019–42030PubMedPubMedCentralGoogle Scholar
  215. Zheng F, Grandy DK, Johnson SW (2002) Actions of orphanin fq/nociceptin on rat ventral tegmental area neurons in vitro. Br J Pharmacol 136:1065–1071PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bryony L. Winters
    • 1
    Email author
  • Macdonald J. Christie
    • 2
  • Christopher W. Vaughan
    • 1
  1. 1.Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, Faculty of Medicine and HealthThe University of Sydney and Royal North Shore HospitalSt LeonardsAustralia
  2. 2.Discipline of Pharmacology, Faculty of Medicine and HealthThe University of SydneyCamperdownAustralia

Personalised recommendations