PAIN
Volume 148, Issue 3 , Pages 414-425 , March 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

  • Ning Lü

      Affiliations

    • These authors contributed equally to this work.
  • ,
  • Mei Han

      Affiliations

    • These authors contributed equally to this work.
  • ,
  • Zhi-Lan Yang
  • ,
  • Yan-Qing Wang
  • ,
  • Gen-Cheng Wu

      Affiliations

    • Corresponding Author InformationCorresponding authors. Address: Institute of Neurobiology, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China. Tel.: +86 21 54237635; fax: +86 21 54237647.
  • ,
  • Yu-Qiu Zhang

      Affiliations

    • Corresponding Author InformationCorresponding authors. Address: Institute of Neurobiology, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China. Tel.: +86 21 54237635; fax: +86 21 54237647.

Received 15 April 2009 ,Revised 28 October 2009 ,Accepted 30 November 2009.

References 

  1. Aimone LD, Jones SL, Gebhart GF. Stimulation-produced descending inhibition from the periaqueductal gray and nucleus raphe magnus in the rat: mediation by spinal monoamines but not opioids. Pain. 1987;31:123–136
  2. Bajic D, Van Bockstaele EJ, Proudfit HK. Ultrastructural analysis of ventrolateral periaqueductal gray projections to the A7 catecholamine cell group. Neuroscience. 2001;104:181–197
  3. Bajic D, Proudfit HK. Projections of neurons in the periaqueductal gray to pontine and medullary catecholamine cell groups involved in the modulation of nociception. J Comp Neurol. 1999;405:359–379
  4. Basbaum AI, Fields HL. The origin of descending pathways in the dorsolateral funiculus of the spinal cord of the cat and rat: further studies on the anatomy of pain modulation. J Comp Neurol. 1979;187:513–531
  5. Basbaum AI, Fields HL. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci. 1984;7:309–338
  6. Beitz AJ. Relationship of glutamate and aspartate to the periaqueductal gray-raphe magnus projection: analysis using immunocytochemistry and microdialysis. J Histochem Cytochem. 1990;38:1755–1765
  7. Bunzow JR, Saez C, Mortrud M, Bouvier C, Williams JT, Low M, et al. Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not a mu, delta or kappa opioid receptor type. FEBS Lett. 1994;347:284–288
  8. Cameron AA, Khan IA, Westlund KN, Willis WD. The efferent projections of the periaqueductal gray in the rat: a Phaseolus vulgaris-leucoagglutinin study. II. Descending projections.. J Comp Neurol. 1995;351:585–601
  9. Christie MJ, Connor M, Vaughan CW, Ingram SL, Bagley EE. Cellular actions of opioids and other analgesics: implications for synergism in pain relief. Clin Exp Pharmacol Physiol. 2000;27:520–523
  10. Clark FM, Proudfit HK. The projections of noradrenergic neurons in the A5 catecholamine cell group to the spinal cord in the rat: anatomical evidence that A5 neurons modulate nociception. Brain Res. 1993;616:200–210
  11. Cui M, Feng Y, McAdoo DJ, Willis WD. Periaqueductal gray stimulation-induced inhibition of nociceptive dorsal horn neurons in rats is associated with the release of norepinephrine, serotonin, and amino acids. J Pharmacol Exp Ther. 1999;289:868–876
  12. Darland T, Heinricher MM, Grandy DK. Orphanin FQ/nociceptin: a role in pain and analgesia, but so much more. Trends Neurosci. 1998;21:215–221
  13. Dubner R, Bennett GJ. Spinal and trigeminal mechanisms of nociception. Annu Rev Neurosci. 1983;6:381–418
  14. Fields HL, Basbaum AI. Brainstem control of spinal pain-transmission neurons. Annu Rev Physiol. 1978;40:217–248
  15. Fields HL, Basbaum AI. Central nervous system mechanisms of pain modulation. In:  Wall PD,  Melzack R editor. Textbook of Pain. 4th ed.. Edinburgh: Chruchill Livingston; 1999;p. 309–329
  16. Fields HL, Heinricher MM, Mason P. Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci. 1991;14:219–245
  17. Florin S, Meunier J, Costentin J. Autoradiographic localization of [3H]nociceptin binding sites in the rat brain. Brain Res. 2000;880:11–16
  18. Gao K, Kim YH, Mason P. Serotonergic pontomedullary neurons are not activated by antinociceptive stimulation in the periaqueductal gray. J Neurosci. 1997;17:3285–3292
  19. Gebhart GF, Ossipov MH. Characterization of inhibition of the spinal nociceptive tail-flick reflex in the rat from the medullary lateral reticular nucleus. J Neurosci. 1986;6:701–713
  20. Grisel JE, Mogil JS, Belknap JK, Grandy DK. Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide. Neuroreport. 1996;7:2125–2129
  21. Haber LH, Martin RF, Chung JM, Willis WD. Inhibition and excitation of primate spinothalamic tract neurons by stimulation in region of nucleus reticularis gigantocellularis. J Neurophysiol. 1980;43:1578–1593
  22. Hammond DL, Tyce GM, Yaksh TL. Efflux of 5-hydroxytryptamine and noradrenaline into spinal cord superfusates during stimulation of the rat medulla. J Physiol. 1985;359:151–162
  23. Hawes BE, Graziano MP, Lambert DG. Cellular actions of nociceptin: transduction mechanisms. Peptides. 2000;21:961–967
  24. Heinricher MM. Orphanin FQ/nociceptin: from neural circuitry to behavior. Life Sci. 2003;73:813–822
  25. Heinricher MM. Nociceptin/orphanin FQ: pain, stress and neural circuits. Life Sci. 2005;77:3127–3132
  26. Henderson G, McKnight AT. The orphan opioid receptor and its endogenous ligand-nociceptin/orphanin FQ. Trends Pharmacol Sci. 1997;18:293–300
  27. Hernández N, Vanegas H. Antinociception induced by PAG-microinjected dipyrone (metamizol) in rats: involvement of spinal endogenous opioids. Brain Res. 2001;896:175–178
  28. Jones BE, Holmes CJ, Rodriguez-Veiga E, Mainville L. GABA-synthesizing neurons in the medulla: their relationship to serotonin-containing and spinally projecting neurons in the rat. J Comp Neurol. 1991;313:349–367
  29. Kerchner GA, Wang GD, Qiu CS, Huettner JE, Zhuo M. Direct presynaptic regulation of GABA/glycine release by kainate receptors in the dorsal horn: an ionotropic mechanism. Neuron. 2001;32:477–488
  30. Kwiat GC, Basbaum AI. The origin of brainstem noradrenergic and serotonergic projections to the spinal cord dorsal horn in the rat. Somatosens Mot Res. 1992;9:157–173
  31. Lakos S, Basbaum AI. An ultrastructural study of the projections from the midbrain periaqueductal gray to spinally projecting, serotonin-immunoreactive neurons of the medullary nucleus raphe magnus in the rat. Brain Res. 1988;443:383–388
  32. Le Maître E, Vilpoux C, Costentin J, Leroux-Nicollet I. Opioid receptor-like 1 (NOP) receptors in the rat dorsal raphe nucleus: evidence for localization on serotoninergic neurons and functional adaptation after 5,7-dihydroxytryptamine lesion. J Neurosci Res. 2005;81:488–496
  33. Lin Q, Peng Y, Willis WD. Glycine and GABAA antagonists reduce the inhibition of primate spinothalamic tract neurons produced by stimulation in periaqueductal gray. Brain Res. 1994;654:286–302
  34. Lin Q, Peng YB, Willis WD. Antinociception and inhibition from the periaqueductal gray are mediated in part by spinal 5-hydroxytryptamine(1A) receptors. J Pharmacol Exp Ther. 1996;276:958–967
  35. Mason P. Deconstructing endogenous pain modulations. J Neurophysiol. 2005;94:1659–1663
  36. Martin GF, Cabana T, DiTirro FJ, Ho RH, Humbertson AO. Reticular and raphe projections to the spinal cord of the North American opossum. Evidence for connectional heterogeneity. Prog Brain Res. 1982;57:109–129
  37. McCreery DB, Bloedel JR, Hames EG. Effects of stimulating in raphe nuclei and in reticular formation on response of spinothalamic neurons to mechanical stimuli. J Neurophysiol. 1979;42:166–182
  38. McMahon SB, Wall PD. Descending excitation and inhibition of spinal cord lamina I projection neurons. J Neurophysiol. 1988;59:1204–1219
  39. Meng XW, Budra B, Skinner K, Ohara PT, Fields HL. Noradrenergic input to nociceptive modulatory neurons in the rat rostral ventromedial medulla. J Comp Neurol. 1997;377:381–391
  40. Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, et al. Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature. 1995;377:532–535
  41. Meunier JC. Utilizing functional genomics to identify new pain treatments: the example of nociceptin. Am J Pharmacogenomics. 2003;3:117–130
  42. Millan MJ. The induction of pain: an integrative review. Prog Neurobiol. 1999;57:1–164
  43. Millan MJ. Descending control of pain. Prog Neurobiol. 2002;66:355–474
  44. Mogil JS, Grisel JE, Zhangs G, Belknap JK, Grandy DK. Functional antagonism of mu-, delta- and kappa-opioid antinociception by orphanin FQ. Neurosci Lett. 1996;214:131–134
  45. Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, et al. ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. FEBS Lett. 1994;341:33–38
  46. Moran TD, Abdulla FA, Smith PA. Cellular neurophysiological actions of nociceptin/orphanin FQ. Peptides. 2000;21:969–976
  47. Morgan MM, Grisel JE, Robbins CS, Grandy DK. Antinociception mediated by the periaqueductal gray is attenuated by orphanin FQ. Neuroreport. 1997;8:3431–3434
  48. Morgan MM, Whittier KL, Hegarty DM, Aicher SA. Periaqueductal gray neurons project to spinally projecting GABAergic neurons in the rostral ventromedial medulla. Pain. 2008;140:376–386
  49. Neal CR, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Akil H, et al. 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. 1999;412:563–605
  50. Pan ZZ, Wessendorf MW, Williams JT. Modulation by serotonin of the neurons in rat nucleus raphe magnus in vitro. Neuroscience. 1993;54:421–429
  51. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. New York: Academic Press; 1998;
  52. Peng YB, Lin Q, Willis WD. Involvement of alpha-2 adrenoceptors in the periaqueductal gray-induced inhibition of dorsal horn cell activity in rats. J Pharmacol Exp Ther. 1996;278:125–135
  53. Peng YB, Lin Q, Willis WD. The role of 5-HT3 receptors in periaqueductal gray-induced inhibition of nociceptive dorsal horn neurons in rats. J Pharmacol Exp Ther. 1996;276:116–124
  54. Peng YB, Lin Q, Willis WD. Effects of GABA and glycine receptor antagonists on the activity and PAG-induced inhibition of rat dorsal horn neurons. Brain Res. 1996;736:189–201
  55. Reichling DB, Basbaum AI. Contribution of brainstem GABAergic circuitry to descending antinociceptive controls: I. GABA-immunoreactive projection neurons in the periaqueductal gray and nucleus raphe magnus. J Comp Neurol. 1990;302:370–377
  56. Reinscheid RK, Nothacker HP, Bourson A, Ardati A, Henningsen RA, Bunzow JR, et al. Orphanin FQ: a neuropeptide that activates an opioidlike G protein-coupled receptor. Science. 1995;270:792–794
  57. Riedl M, Shuster S, Vulchanova L, Wang J, Loh HH, Elde R. Orphanin FQ/nociceptin-immunoreactive nerve fibers parallel those containing endogenous opioids in rat spinal cord. Neuroreport. 1996;7:1369–1372
  58. Rosin DL, Zeng D, Stornetta RL, Norton FR, Riley T, Okusa MD, et al. Immunohistochemical localization of alpha 2A-adrenergic receptors in catecholaminergic and other brainstem neurons in the rat. Neuroscience. 1993;56:139–155
  59. Sbrenna S, Marti M, Morari M, Calo’ G, Guerrini R, Beani L, et al. Modulation of 5-hydroxytryptamine efflux from rat cortical synaptosomes by opioids and nociceptin. Br J Pharmacol. 2000;130:425–433
  60. Schlicker E, Morari M. Nociceptin/orphanin FQ and neurotransmitter release in the central nervous system. Peptides. 2000;21:1023–1029
  61. Scoto GM, Aricò G, Ronsisvalle S, Parenti C. Blockade of the nociceptin/orphanin FQ/NOP receptor system in the rat ventrolateral periaqueductal gray potentiates DAMGO analgesia. Peptides. 2007;28:1441–1446
  62. Sorkin LS, McAdoo DJ, Willis WD. Raphe magnus stimulation-induced antinociception in the cat is associated with release of amino acids as well as serotonin in the lumbar dorsal horn. Brain Res. 1993;618:95–108
  63. Thomas DA, McGowan MK, Hammond DL. Microinjection of baclofen in the ventromedial medulla of rats: antinociception at low doses and hyperalgesia at high doses. J Pharmacol Exp Ther. 1995;275:274–284
  64. Tian JH, Xu W, Fang Y, Mogil JS, Grisel JE, Grandy DK, et al. Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat. Br J Pharmacol. 1997;120:676–680
  65. Tian JH, Xu W, Zhang W, Fang Y, Grisel JE, Mogil JS, et al. Involvement of endogenous orphanin FQ in electroacupuncture-induced analgesia. Neuroreport. 1997;8:497–500
  66. Urban MO, Gebhart GF. Characterization of biphasic modulation of spinal nociceptive transmission by neurotensin in the rat rostral ventromedial medulla. J Neurophysiol. 1997;78:1550–1562
  67. Urban MO, Smith DJ. Role of neurotensin in the nucleus raphe magnus in opioid-induced antinociception from the periaqueductal gray. J Pharmacol Exp Ther. 1993;265:580–586
  68. Varga V, Székely AD, Csillag A, Sharp T, Hajós M. Evidence for a role of GABA interneurones in the cortical modulation of midbrain 5-hydroxytryptamine neurones. Neuroscience. 2001;106:783–792
  69. Wang H, Zhu CB, Cao XD, Wu GC. Effect of orphanin FQ on acupuncture analgesia and noxious stimulation in the periaqueductal gray. Acta Physiol Sin. 1998;50:263–267
  70. Wang JL, Zhu CB, Cao XD, Wu GC. Distinct effect of intracerebroventricular and intrathecal injections of nociceptin/orphanin FQ in the rat formalin test. Regul Pept. 1999;79:159–163
  71. Wang YQ, Zhu CB, Wu GC, Cao XD, Wang Y, Cui DF. Effects of orphanin FQ on endomorphin-1 induced analgesia. Brain Res. 1999;835:241–246
  72. Wei F, Dubner R, Ren K. Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation. Pain. 1999;80:127–141
  73. Willcockson WS, Chung JM, Hori Y, Lee KH, Willis WD. Effects of iontophoretically released amino acids and amines on primate spinothalamic tract cells. J Neurosci. 1984;4:732–740
  74. Yang HL, Luo RS, Wang LX, Zhu DX, Chi CW. Primary structure and disulfide bridge location of arrowhead double-headed proteinase inhibitors. J Biochem. 1992;111:537–545
  75. Yang ZL, Gao YJ, Wu GC, Zhang YQ. The rostral ventromedial medulla mediates the facilitatory effect of microinjected orphanin FQ in the periaqueductal gray on spinal nociceptive transmission in rats. Neuropharmacology. 2003;45:612–622
  76. Yang ZL, Zhang YQ, Wu GC. Effects of microinjection of OFQ into PAG on spinal dorsal horn WDR neurons in rats. Brain Res. 2001;888:167–171
  77. Yang Z, Zhang Y, Wu G. Distinct effect of orphanin FQ in nucleus raphe magnus and nucleus reticularis gigantocellularis on the rat tail flick reflex. Neurosci Lett. 2001;306:69–72
  78. Zhang YQ, Gao X, Zhang LM, Wu GC. The release of serotonin in rat spinal dorsal horn and periaqueductal gray following carrageenan inflammation. Neuroreport. 2000;11:3539–3543
  79. Zhang Y, Yang Z, Gao X, Wu G. The role of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors in modulating spinal nociceptive transmission in normal and carrageenan-injected rats. Pain. 2001;92:201–211
  80. Zhuo M, Gebhart GF. Characterization of descending inhibition and facilitation from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. Pain. 1990;42:337–350
  81. Zhuo M, Gebhart GF. Characterization of descending facilitation and inhibition of spinal nociceptive transmission from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. J Neurophysiol. 1992;67:1599–1614

PII: S0304-3959(09)00717-9

doi: 10.1016/j.pain.2009.11.025

PAIN
Volume 148, Issue 3 , Pages 414-425 , March 2010