Synaptic modulation in pain pathways

Part of the Reviews of Physiology, Biochemistry and Pharmacology book series (REVIEWS, volume 154)


All higher organisms possess a sensory system that allows them to detect potentially tissue-damaging (or noxious) stimuli. The proper functioning of this system is essential to protect their bodies from tissue damage. However, under pathological conditions after severe tissue injury and in inflammatory or neuropathic diseases, this system can become sensitized, and pain can then turn into a disease. Such exaggerated pain sensation (or hyperalgesia) can arise at different levels of integration. It can originate from an increased responsiveness of primary nociceptors, specialized nerve cells, which sense noxious stimuli, or from changes in the central processing of nociceptive input. Like other sensory input, nociceptive signals are relayed in the central nervous system by neurons, which communicate with each other mainly through chemical synapses. Changes in the excitability of these neurons or in the strength of their synaptic coupling provide the cellular basis for many forms of pathological pain. This review focuses on the synaptic processing of pain-related signals in the spinal cord dorsal horn, the first site of synaptic integration in the pain pathway. Particular emphasis is paid to synaptic processes underlying the generation of pathological pain evoked by inflammation or neuropathic diseases.


NMDA Receptor Neuropathic Pain Dorsal Horn AMPA Receptor GABAB Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Ahmadi S, Kotalla C, Gühring H, Takeshima H, Pahl A, Zeilhofer HU (2001) 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
  2. Ahmadi S, Lippross S, Neuhuber WL, Zeilhofer HU (2002) PGE2 selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons. Nat Neurosci 5:34–40PubMedGoogle Scholar
  3. Ahmadi S, Muth-Selbach U, Lauterbach A, Lipfert P, Neuhuber WL, Zeilhofer HU (2003) Facilitation of spinal NMDA receptor currents by spillover of synaptically released glycine. Science 300:2094–2097PubMedGoogle Scholar
  4. Albuquerque C, Lee CJ, Jackson AC, MacDermott AB (1999) Subpopulations of GABAergic and non-GABAergic rat dorsal horn neurons express Ca2+-permeable AMPA receptors. Eur J Neurosci 11:2758–2766PubMedGoogle Scholar
  5. Antal M, Petko M, Polgar E, Heizmann CW, Storm-Mathisen J (1996) Direct evidence of an extensive GABAergic innervation of the spinal dorsal horn by fibres descending from the rostral ventromedial medulla. Neuroscience 73:509–518PubMedGoogle Scholar
  6. Ataka T, Kumamoto E, Shimoji K, Yoshimura M (2000) Baclofen inhibits more effectively C-afferent than Adelta-afferent glutamatergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices. Pain 86:273–282PubMedGoogle Scholar
  7. Azkue JJ, Liu XG, Zimmermann M, Sandkuhler J (2003) Induction of long-term potentiation of C fibre-evoked spinal field potentials requires recruitment of group I, but not group II/III metabotropic glutamate receptors. Pain 106:373–379PubMedGoogle Scholar
  8. Baba H, Doubell TP, Moore KA, Woolf CJ (2000a) Silent NMDA receptor-mediated synapses are developmentally regulated in the dorsal horn of the rat spinal cord. J Neurophysiol 83:955–962PubMedGoogle Scholar
  9. Baba H, Goldstein PA, Okamoto M, Kohno T, Ataka T, Yoshimura M, Shimoji K (2000b) Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord. II. Effects on somatodendritic sites of GABAergic neurons. Anesthesiology 92:485–492PubMedGoogle Scholar
  10. Baba H, Shimoji K, Yoshimura M (2000c) Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord. I. Effects on axon terminals of GABAergic and glycinergic neurons. Anesthesiology 92:473–484PubMedGoogle Scholar
  11. Baba H, Kohno T, Moore KA, Woolf CJ (2001) Direct activation of rat spinal dorsal horn neurons by prostaglandin E2. J Neurosci 21:1750–1756PubMedGoogle Scholar
  12. Bär KJ, Natura G, Telleria-Diaz A, Teschner P, Vogel R, Vasquez E, Schaible HG, Ebersberger A (2004) Changes in the effect of spinal prostaglandin E2 during inflammation: prostaglandin E (EP1-EP4) receptors in spinal nociceptive processing of input from the normal or inflamed knee joint. J Neurosci 24:642–651PubMedGoogle Scholar
  13. Bardoni R, Goldstein PA, Lee CJ, Gu JG, MacDermott AB (1997) ATP P2X receptors mediate fast synaptic transmission in the dorsal horn of the rat spinal cord. J Neurosci 17:5297–5304PubMedGoogle Scholar
  14. Bardoni R, Torsney C, Tong CK, Prandini M, MacDermott AB (2004) Presynaptic NMDA receptors modulate glutamate release from primary sensory neurons in rat spinal cord dorsal horn. J Neurosci 24:2774–2781PubMedGoogle Scholar
  15. Barria A, Muller D, Derkach V, Griffith LC, Soderling TR (1997) Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation. Science 276:2042–2045PubMedGoogle Scholar
  16. Basbaum AI, Fields HL (1984) Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 7:309–338PubMedGoogle Scholar
  17. Bayer K, Ahmadi S, Zeilhofer HU (2004) Gabapentin may inhibit synaptic transmission in the mouse spinal cord dorsal horn through a preferential block of P/Q-type Ca2+ channels. Neuropharmacology 46:743–749PubMedGoogle Scholar
  18. Beiche F, Scheuerer S, Brune K, Geisslinger G, Goppelt-Struebe M (1996) Up-regulation of cyclooxygenase-2 mRNA in the rat spinal cord following peripheral inflammation. FEBS Lett 390:165–169PubMedGoogle Scholar
  19. Bennett MI, Simpson KH (2004) Gabapentin in the treatment of neuropathic pain. Palliat Med 18:5–11PubMedGoogle Scholar
  20. Berger AJ, Dieudonne S, Ascher P (1998) Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J Neurophysiol 80:3336–3340PubMedGoogle Scholar
  21. Bergeron R, Meyer TM, Coyle JT, Greene RW (1998) Modulation of N-methyl-D-aspartate receptor function by glycine transport. Proc Natl Acad Sci USA 95:15730–15734PubMedGoogle Scholar
  22. Bowersox SS, Gadbois T, Singh T, Pettus M, Wang YX, Luther RR (1996) Selective N-type neuronal voltage-sensitive calcium channel blocker, SNX-111, produces spinal antinociception in rat models of acute, persistent and neuropathic pain. J Pharmacol Exp Ther 279:1243–1249PubMedGoogle Scholar
  23. Breitinger HG, Becker CM (1998) The inhibitory glycine receptor: prospects for a therapeutic orphan? Curr Pharm Des 4:315–334PubMedGoogle Scholar
  24. Broom DC, Samad TA, Kohno T, Tegeder I, Geisslinger G, Woolf CJ (2004) Cyclooxygenase 2 expression in the spared nerve injury model of neuropathic pain. Neuroscience 124:891–900PubMedGoogle Scholar
  25. Brown JT, Randall A (2005) Gabapentin fails to alter P/Q-type Ca2+ channel-mediated synaptic transmission in the hippocampus. Synapse 55:262–269PubMedGoogle Scholar
  26. Cervero F, Laird JM (1996) Mechanisms of allodynia: interactions between sensitive mechanoreceptors and nociceptors. Neuroreport 7:526–528PubMedGoogle Scholar
  27. Chen J, Heinke B, Sandkühler J (2000) Activation of group I metabotropic glutamate receptors induces long-term depression at sensory synapses in superficial spinal dorsal horn. Neuropharmacology 39:2231–2243PubMedGoogle Scholar
  28. Chen L, Huang LY (1992) Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation. Nature 356:521–523PubMedGoogle Scholar
  29. Chery N, de Koninck Y (1999) Junctional versus extrajunctional glycine and GABAA receptor-mediated IPSCs in identified lamina I neurons of the adult rat spinal cord. J Neurosci 19:7342–7355PubMedGoogle Scholar
  30. Chery N, de Koninck Y (2000) GABAB receptors are the first target of released GABA at lamina I inhibitory synapses in the adult rat spinal cord. J Neurophysiol 84:1006–1011PubMedGoogle Scholar
  31. Chizh BA, Headley PM, Tzschentke TM (2001) NMDA receptor antagonists as analgesics: focus on the NR2B subtype. Trends Pharmacol Sci 22:636–642PubMedGoogle Scholar
  32. Coderre TJ, Melzack R (1987) Cutaneous hyperalgesia: contributions of the peripheral and central nervous systems to the increase in pain sensitivity after injury. Brain Res 404:95–106PubMedGoogle Scholar
  33. Cook AJ, Woolf CJ, Wall PD, McMahon SB (1987) Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input. Nature 325:151–153PubMedGoogle Scholar
  34. Cordero-Erausquin M, Changeux JP (2001) Tonic nicotinic modulation of serotoninergic transmission in the spinal cord. Proc Natl Acad Sci USA 98:2803–2807PubMedGoogle Scholar
  35. Cordero-Erausquin M, Pons S, Faure P, Changeux JP (2004) Nicotine differentially activates inhibitory and excitatory neurons in the dorsal spinal cord. Pain 109:308–318PubMedGoogle Scholar
  36. Coull JA, Boudreau D, Bachand K, Prescott SA, Nault F, Sik A, de Koninck P, de Koninck Y (2003) Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 424:938–942PubMedGoogle Scholar
  37. Depner UB, Reinscheid RK, Takeshima H, Brune K, Zeilhofer HU (2003) Normal sensitivity of acute pain, but increased inflammatory hyperalgesia in mice lacking the nociceptin precursor polypeptide or the nociceptin receptor. Eur J Neurosci 17:2381–2387PubMedGoogle Scholar
  38. Derkach V, Barria A, Soderling TR (1999) Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors. Proc Natl Acad Sci USA 96:3269–3274PubMedGoogle Scholar
  39. Dooley DJ, Donovan CM, Meder WP, Whetzel SZ (2002) Preferential action of gabapentin and pregabalin at P/Q-type voltage-sensitive calcium channels: inhibition of K+-evoked [3H]-norepinephrine release from rat neocortical slices. Synapse 45:171–190PubMedGoogle Scholar
  40. Durand GM, Kovalchuk Y, Konnerth A (1996) Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381:71–75PubMedGoogle Scholar
  41. Engelman HS, Allen TB, MacDermott AB (1999) The distribution of neurons expressing calcium-permeable AMPA receptors in the superficial laminae of the spinal cord dorsal horn. J Neurosci 19:2081–2089PubMedGoogle Scholar
  42. Erb K, Liebel JT, Tegeder I, Zeilhofer HU, Brune K, Geisslinger G (1997) Spinally delivered nociceptin/orphanin FQ reduces flinching behaviour in the rat formalin test. Neuroreport 8:1967–1970PubMedGoogle Scholar
  43. Esteban JA, Shi SH, Wilson C, Nuriya M, Huganir RL, Malinow R (2003) PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nat Neurosci 6:136–143PubMedGoogle Scholar
  44. Fang L, Wu J, Zhang X, Lin Q, Willis WD (2003) Increased phosphorylation of the GluR1 subunit of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor in rats following intradermal injection of capsaicin. Neuroscience 122:237–245PubMedGoogle Scholar
  45. Fink K, Meder W, Dooley DJ, Göthert M (2000) Inhibition of neuronal Ca2+ influx by gabapentin and subsequent reduction of neurotransmitter release from rat neocortical slices. Br J Pharmacol 130:900–906PubMedGoogle Scholar
  46. Fink K, Dooley DJ, Meder WP, Suman-Chauhan N, Duffy S, Clusmann H, Göthert M (2002) Inhibition of neuronal Ca2+ influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology 42:229–236PubMedGoogle Scholar
  47. Flores CM (2000) The promise and pitfalls of a nicotinic cholinergic approach to pain management. Pain 88:1–6PubMedGoogle Scholar
  48. Gabernet L, Pauly-Evers M, Schwerdel C, Lentz M, Bluethmann H, Vogt K, Alberati D, Möhler H, Boison D (2005) Enhancement of the NMDA receptor function by reduction of glycine transporter-1 expression. Neurosci Lett 373:79–84PubMedGoogle Scholar
  49. Galan A, Laird JM, Cervero F (2004) In vivo recruitment by painful stimuli of AMPA receptor subunits to the plasma membrane of spinal cord neurons. Pain 112:315–323PubMedGoogle Scholar
  50. Garraway SM, Hochman S (2001) Serotonin increases the incidence of primary afferent-evoked long-term depression in rat deep dorsal horn neurons. J Neurophysiol 85:1864–1872PubMedGoogle Scholar
  51. Gassmann M, Shaban H, Vigot R, Sansig G, Haller C, Barbieri S, Humeau Y, Schuler V, Muller M, Kinzel B, Klebs K, Schmutz M, Froestl W, Heid J, Kelly PH, Gentry C, Jaton AL, Van der Putten H, Mombereau C, Lecourtier L, Mosbacher J, Cryan JF, Fritschy JM, Luthi A, Kaupmann K, Bettler B (2004) Redistribution of GABAB1 protein and atypical GABAB responses in GABAB2-deficient mice. J Neurosci 24:6086–6097PubMedGoogle Scholar
  52. Gerevich Z, Borvendeg SJ, Schroder W, Franke H, Wirkner K, Norenberg W, Furst S, Gillen C, Illes P (2004) Inhibition of N-type voltage-activated calcium channels in rat dorsal root ganglion neurons by P2Y receptors is a possible mechanism of ADP-induced analgesia. J Neurosci 24:797–807PubMedGoogle Scholar
  53. Goodchild CS, Serrao JM (1987) Intrathecal midazolam in the rat: evidence for spinally-mediated analgesia. Br J Anaesth 59:1563–1570PubMedGoogle Scholar
  54. Grisel JE, Mogil JS, Belknap JK, Grandy DK (1996) Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide. Neuroreport 7:2125–2129PubMedGoogle Scholar
  55. Grudt TJ, Henderson G (1998) Glycine and GABAA receptor-mediated synaptic transmission in rat substantia gelatinosa: inhibition by μ-opioid and GABAB agonists. J Physiol 507:473–483PubMedGoogle Scholar
  56. Gu JG, MacDermott AB (1997) Activation of ATP P2X receptors elicits glutamate release from sensory neuron synapses. Nature 389:749–753PubMedGoogle Scholar
  57. Gu JG, Albuquerque C, Lee CJ, MacDermott AB (1996) Synaptic strengthening through activation of Ca2+-permeable AMPA receptors. Nature 381:793–796PubMedGoogle Scholar
  58. Gu Y, Huang LY (2002) Gabapentin potentiates N-methyl-D-aspartate receptor mediated currents at GABAergic dorsal horn neurons. Neurosci Lett 324:177–180PubMedGoogle Scholar
  59. Guay J, Bateman K, Gordon R, Mancini J, Riendeau D (2004) Carrageenan-induced paw edema in rat elicits a predominant prostaglandin E2 (PGE2) response in the central nervous system associated with the induction of microsomal PGE2 synthase-1. J Biol Chem 279:24866–24872PubMedGoogle Scholar
  60. Guo W, Wei F, Zou S, Robbins MT, Sugiyo S, Ikeda T, Tu JC, Worley PF, Dubner R, Ren K (2004) Group I metabotropic glutamate receptor NMDA receptor coupling and signaling cascade mediate spinal dorsal horn NMDA receptor 2B tyrosine phosphorylation associated with inflammatory hyperalgesia. J Neurosci 24:9161–9173PubMedGoogle Scholar
  61. Harris J, Drew LJ, Chapman V (2000) Spinal anandamide inhibits nociceptive transmission via cannabinoid receptor activation in vivo. Neuroreport 11:2817–2819PubMedGoogle Scholar
  62. Hartmann B, Ahmadi S, Heppenstall PA, Lewin GR, Schott C, Borchardt T, Seeburg PH, Zeilhofer HU, Sprengel R, Kuner R (2004) The AMPA receptor subunits GluR-A and GluR-B reciprocally modulate spinal synaptic plasticity and inflammatory pain. Neuron 44:637–650PubMedGoogle Scholar
  63. Harvey RJ, Depner UB, Wässle H, Ahmadi S, Heindl C, Reinold H, Smart TG, Harvey K, Schütz B, Abo-Salem OM, Zimmer A, Poisbeau P, Welzl H, Wolfer DP, Betz H, Zeilhofer HU, Müller U (2004) GlyR α3: an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science 304:884–887PubMedGoogle Scholar
  64. Hebb DO (1966) A textbook of psychology. Saunders, PhiladelphiaGoogle Scholar
  65. Hori Y, Endo K, Takahashi T (1996) Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of the rat spinal cord. J Physiol 492:867–876PubMedGoogle Scholar
  66. Hugel S, Schlichter R (2000) Presynaptic P2X receptors facilitate inhibitory GABAergic transmission between cultured rat spinal cord dorsal horn neurons. J Neurosci 20:2121–2130PubMedGoogle Scholar
  67. Hugel S, Schlichter R (2003) Convergent control of synaptic GABA release from rat dorsal horn neurones by adenosine and GABA autoreceptors. J Physiol 551:479–489PubMedGoogle Scholar
  68. Hunter JC, Fontana DJ, Hedley LR, Jasper JR, Lewis R, Link RE, Secchi R, Sutton J, Eglen RM (1997) Assessment of the role of alpha2-adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice. Br J Pharmacol 122:1339–1344PubMedGoogle Scholar
  69. Hwang SJ, Pagliardini S, Rustioni A, Valtschanoff JG (2001) Presynaptic kainate receptors in primary afferents to the superficial laminae of the rat spinal cord. J Comp Neurol 436:275–289PubMedGoogle Scholar
  70. Ikeda H, Heinke B, Ruschewey R, Sandkühler J (2003) Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science 299:1237–1240PubMedGoogle Scholar
  71. Iyadomi M, Iyadomi I, Kumamoto E, Tomokuni K, Yoshimura M (2000) Presynaptic inhibition by baclofen of miniature EPSCs and IPSCs in substantia gelatinosa neurons of the adult rat spinal dorsal horn. Pain 85:385–393PubMedGoogle Scholar
  72. Jang IS, Rhee JS, Kubota H, Akaike N (2001) Developmental changes in P2X purinoceptors on glycinergic presynaptic nerve terminals projecting to rat substantia gelatinosa neurones. J Physiol 536:505–519PubMedGoogle Scholar
  73. Jasmin L, Wu MV, Ohara PT (2004) GABA puts a stop to pain. Curr Drug Targets CNS Neurol Disord 3:487–505PubMedGoogle Scholar
  74. Ji RR, Kohno T, Moore KA, Woolf CJ (2003) Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 26:696–705PubMedGoogle Scholar
  75. Jo YH, Schlichter R (1999) Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosci 2:241–245PubMedGoogle Scholar
  76. Johnson JW, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325:529–531PubMedGoogle Scholar
  77. Jun JH, Yaksh TL (1998) The effect of intrathecal gabapentin and 3-isobutyl gamma-aminobutyric acid on the hyperalgesia observed after thermal injury in the rat. Anesth Analg 86:348–354PubMedGoogle Scholar
  78. Kable JW, Murrin LC, Bylund DB (2000) In vivo gene modification elucidates subtype-specific functions of α2-adrenergic receptors. J Pharmacol Exp Ther 293:1–7PubMedGoogle Scholar
  79. Kamei D, Yamakawa K, Takegoshi Y, Mikami-Nakanishi M, Nakatani Y, Oh-Ishi S, Yasui H, Azuma Y, Hirasawa N, Ohuchi K, Kawaguchi H, Ishikawa Y, Ishii T, Uematsu S, Akira S, Murakami M, Kudo I (2004) Reduced pain hypersensitivity and inflammation in mice lacking microsomal prostaglandin E synthase-1. J Biol Chem 279:33684–33695PubMedGoogle Scholar
  80. Kaneko M, Mestre C, Sanchez EH, Hammond DL (2000) Intrathecally administered gabapentin inhibits formalin-evoked nociception and Fos-like immunoreactivity in the spinal cord of the rat. J Pharmacol Exp Ther 292:743–751PubMedGoogle Scholar
  81. Kawasaki Y, Kumamoto E, Furue H, Yoshimura M (2003) α2 adrenoceptor-mediated presynaptic inhibition of primary afferent glutamatergic transmission in rat substantia gelatinosa neurons. Anesthesiology 98:682–689PubMedGoogle Scholar
  82. Keller AF, Coull JA, Chery N, Poisbeau P, de Koninck Y (2001) Region-specific developmental specialization of GABA-glycine cosynapses in laminas I-II of the rat spinal dorsal horn. J Neurosci 21:7871–7880PubMedGoogle Scholar
  83. Kelly S, Chapman V (2001) Selective cannabinoid CB1 receptor activation inhibits spinal nociceptive transmission in vivo. J Neurophysiol 86:3061–3064PubMedGoogle Scholar
  84. Kerchner GA, Wang GD, Qiu CS, Huettner JE, Zhuo M (2001a) Direct presynaptic regulation of GABA/glycine release by kainate receptors in the dorsal horn: an ionotropic mechanism. Neuron 32:477–488PubMedGoogle Scholar
  85. Kerchner GA, Wilding TJ, Li P, Zhuo M, Huettner JE (2001b) Presynaptic kainate receptors regulate spinal sensory transmission. J Neurosci 21:59–66PubMedGoogle Scholar
  86. Khasabov SG, Lopez-Garcia JA, Asghar AU, King AE (1999) Modulation of afferent-evoked neurotransmission by 5-HT3 receptors in young rat dorsal horn neurones in vitro: a putative mechanism of 5-HT3 induced anti-nociception. Br J Pharmacol 127:843–852PubMedGoogle Scholar
  87. Khasabov SG, Rogers SD, Ghilardi JR, Peters CM, Mantyh PW, Simone DA (2002) Spinal neurons that possess the substance P receptor are required for the development of central sensitization. J Neurosci 22:9086–9098PubMedGoogle Scholar
  88. Kiyosawa A, Katsurabayashi S, Akaike N, Pang ZP, Akaike N (2001) Nicotine facilitates glycine release in the rat spinal dorsal horn. J Physiol 536:101–110PubMedGoogle Scholar
  89. Kleckner NW, Dingledine R (1988) Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes. Science 241:835–837PubMedGoogle Scholar
  90. Klein T, Magerl W, Hopf HC, Sandkühler J, Treede RD (2004) Perceptual correlates of nociceptive long-term potentiation and long-term depression in humans. J Neurosci 24:964–971PubMedGoogle Scholar
  91. Klugbauer N, Marais E, Hofmann F (2003) Calcium channel α2δ subunits: differential expression, function, and drug binding. J Bioenerg Biomembranes 35:639–647Google Scholar
  92. Kohno T, Kumamoto E, Higashi H, Shimoji K, Yoshimura M (1999) Actions of opioids on excitatory and inhibitory transmission in substantia gelatinosa of adult rat spinal cord. J Physiol 518:803–813Google Scholar
  93. Krogsgaard-Larsen P, Frolund B, Liljefors T, Ebert B (2004) GABAA agonists and partial agonists: THIP (Gaboxadol) as a non-opioid analgesic and a novel type of hypnotic. Biochem Pharmacol 68:1573–1580PubMedGoogle Scholar
  94. Lakhlani PP, Macmillan LB, Guo TZ, McCool BA, Lovinger DM, Maze M, Limbird LE (1997) Substitution of a mutant α2a-adrenergic receptor via “hit and run” gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. Proc Natl Acad Sci USA 94:9950–9955PubMedGoogle Scholar
  95. Lao LJ, Kawasaki Y, Yang K, Fujita T, Kumamoto E (2004) Modulation by adenosine of Aδ and C primary-afferent glutamatergic transmission in adult rat substantia gelatinosa neurons. Neuroscience 125:221–231PubMedGoogle Scholar
  96. Laube B, Maksay G, Schemm R, Betz H (2002) Modulation of glycine receptor function: a novel approach for therapeutic intervention at inhibitory synapses? Trends Pharmacol Sci 23:519–527PubMedGoogle Scholar
  97. Lee TL, Fung FM, Chen FG, Chou N, Okuda-Ashitaka E, Ito S, Nishiuchi Y, Kimura T, Tachibana S (1999) Identification of human, rat and mouse nocistatin in brain and human nocistatin in brain and human cerebrospinal fluid. Neuroreport 10:1537–1541PubMedGoogle Scholar
  98. Legendre P (2001) The glycinergic inhibitory synapse. Cell Mol Life Sci 58:760–793PubMedGoogle Scholar
  99. Li H, Lang B, Kang JF, Li YQ (2000) Serotonin potentiates the response of neurons of the superficial laminae of the rat spinal dorsal horn to gamma-aminobutyric acid. Brain Res Bull 52:559–565PubMedGoogle Scholar
  100. Li P, Zhuo M (1998) Silent glutamatergic synapses and nociception in mammalian spinal cord. Nature 393:695–698PubMedGoogle Scholar
  101. Li P, Calejesan AA, Zhuo M (1998) ATP P2x receptors and sensory synaptic transmission between primary afferent fibers and spinal dorsal horn neurons in rats. J Neurophysiol 80:3356–3360PubMedGoogle Scholar
  102. Li P, Wilding TJ, Kim SJ, Calejesan AA, Huettner JE, Zhuo M (1999) Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord. Nature 397:161–164PubMedGoogle Scholar
  103. 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 121:425–432PubMedGoogle Scholar
  104. Light AR, Willcockson HH (1999) Spinal laminae I-II neurons in rat recorded in vivo in whole cell, tight seal configuration: properties and opioid responses. J Neurophysiol 82:3316–3326PubMedGoogle Scholar
  105. Liu XG, Sandkühler J (1995) Long-term potentiation of C-fiber-evoked potentials in the rat spinal dorsal horn is prevented by spinal N-methyl-D-aspartic acid receptor blockage. Neurosci Lett 191:43–46PubMedGoogle Scholar
  106. Liu H, Wang H, Sheng M, Jan LY, Jan YN, Basbaum AI (1994) Evidence for presynaptic N-methyl-D-aspartate autoreceptors in the spinal cord dorsal horn. Proc Natl Acad Sci USA 91:8383–8387PubMedGoogle Scholar
  107. Liu H, Mantyh PW, Basbaum AI (1997) NMDA-receptor regulation of substance P release from primary afferent nociceptors. Nature 386:721–724PubMedGoogle Scholar
  108. Liu XG, Morton CR, Azkue JJ, Zimmermann M, Sandkühler J (1998) Long-term depression of C-fibre-evoked spinal field potentials by stimulation of primary afferent A delta-fibres in the adult rat. Eur J Neurosci 10:3069–3075PubMedGoogle Scholar
  109. Löw K, Crestani F, Keist R, Benke D, Brünig I, Benson JA, Fritschy JM, Rülicke T, Bluethmann H, Möhler H, Rudolph U (2000) Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290:131–134PubMedGoogle Scholar
  110. Lu CR, Hwang SJ, Phend KD, Rustioni A, Valtschanoff JG (2002) Primary afferent terminals in spinal cord express presynaptic AMPA receptors. J Neurosci 22:9522–9529PubMedGoogle Scholar
  111. Luo ZD, Chaplan SR, Higuera ES, Sorkin LS, Stauderman KA, Williams ME, Yaksh TL (2001) Upregulation of dorsal root ganglion α2δ calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats. J Neurosci 21:1868–1875PubMedGoogle Scholar
  112. Luo C, Kumamoto E, Furue H, Chen J, Yoshimura M (2002a) Nociceptin inhibits excitatory but not inhibitory transmission to substantia gelatinosa neurones of adult rat spinal cord. Neuroscience 109:349–358PubMedGoogle Scholar
  113. Luo ZD, Calcutt NA, Higuera ES, Valder CR, Song YH, Svensson CI, Myers RR (2002b) Injury type-specific calcium channel alpha 2 delta-1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. J Pharmacol Exp Ther 303:1199–1205PubMedGoogle Scholar
  114. Lynch JW (2004) Molecular structure and function of the glycine receptor chloride channel. Physiol Rev 84:1051–1095PubMedGoogle Scholar
  115. Mack V, Burnashev N, Kaiser KM, Rozov A, Jensen V, Hvalby O, Seeburg PH, Sakmann B, Sprengel R (2001) Conditional restoration of hippocampal synaptic potentiation in Glur-A-deficient mice. Science 292:2501–2504PubMedGoogle Scholar
  116. Malmberg AB, Brandon EP, Idzerda RL, Liu H, McKnight GS, Basbaum AI (1997) Diminished inflammation and nociceptive pain with preservation of neuropathic pain in mice with a targeted mutation of the type I regulatory subunit of cAMP-dependent protein kinase. J Neurosci 17:7462–7470PubMedGoogle Scholar
  117. Mantyh PW, Rogers SD, Honore P, Allen BJ, Ghilardi JR, Li J, Daughters RS, Lappi DA, Wiley RG, Simone DA (1997) Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275–279PubMedGoogle Scholar
  118. Mao J, Chen LL (2000) Gabapentin in pain management. Anesth Analg 91:680–687PubMedGoogle Scholar
  119. Marais E, Klugbauer N, Hofmann F (2001) Calcium channel α2δ subunits-structure and gabapentin binding. Mol Pharmacol 59:1243–1248PubMedGoogle Scholar
  120. Matthes HW, Maldonado R, Simonin F, Valverde O, Slowe S, Kitchen I, Befort K, Dierich A, Le Meur M, Dolle P, Tzavara E, Hanoune J, Roques BP, Kieffer BL (1996) Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene. Nature 383:819–823PubMedGoogle Scholar
  121. McKernan RM, Rosahl TW, Reynolds DS, Sur C, Wafford K, Atack JR, Farrar S, Myers J, Cook G, Ferris P, Garrett L, Bristow L, Marshall G, Macaulay A, Brown N, Howell O, Moore KW, Carling RW, Street LJ, Castro JL, Ragan CI, Dawson GR, Whiting PJ (2000) Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABAA receptor alpha1 subtype. Nat Neurosci 3:587–592PubMedGoogle Scholar
  122. Meder WP, Dooley DJ (2000) Modulation of K+-induced synaptosomal calcium influx by gabapentin. Brain Res 875:157–159PubMedGoogle Scholar
  123. Mendell LM (1966) Physiological properties of unmyelinated fiber projections to the spinal cord. Exp Neurol 16:316–332PubMedGoogle Scholar
  124. Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, Butour JL, Guillemot JC, Ferrara P, Monsarrat B, Marzarguil H, Vassart G, Parmentier M, Costentin J (1995) Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 377:532–535PubMedGoogle Scholar
  125. Miljanich GP (2004) Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Curr Med Chem 11:3029–3040PubMedGoogle Scholar
  126. Minami T, Okuda-Ashitaka E, Hori Y, Sakuma S, Sugimoto T, Sakimura K, Mishina M, Ito S (1999) Involvement of primary afferent C-fibres in touch-evoked pain (allodynia) induced by prostaglandin E2. Eur J Neurosci 11:1849–1856PubMedGoogle Scholar
  127. Mitrovic I, Margeta-Mitrovic M, Bader S, Stoffel M, Jan LY, Basbaum AI (2003) Contribution of GIRK2-mediated postsynaptic signaling to opiate and alpha 2-adrenergic analgesia and analgesic sex differences. Proc Natl Acad Sci USA 100:271–276PubMedGoogle Scholar
  128. Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, Caput D, Vassart G, Meunier JC (1994) ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. FEBS Lett 341:33–38PubMedGoogle Scholar
  129. Moore KA, Baba H, Woolf CJ (2002a) Gabapentin-actions on adult superficial dorsal horn neurons. Neuropharmacology 43:1077–1081PubMedGoogle Scholar
  130. Moore KA, Kohno T, Karchewski LA, Scholz J, Baba H, Woolf CJ (2002b) Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J Neurosci 22:6724–6731PubMedGoogle Scholar
  131. Morisset V, Urban L (2001) Cannabinoid-induced presynaptic inhibition of glutamatergic EPSCs in substantia gelatinosa neurons of the rat spinal cord. J Neurophysiol 86:40–48PubMedGoogle Scholar
  132. Murakami M, Fleischmann B, De Felipe C, Freichel M, Trost C, Ludwig A, Wissenbach U, Schwegler H, Hofmann F, Hescheler J, Flockerzi V, Cavalie A (2002) Pain perception in mice lacking the β3 subunit of voltage-activated calcium channels. J Biol Chem 277:40342–44051PubMedGoogle Scholar
  133. Muth-Selbach U, Dybek E, Kollosche K, Stegmann JU, Holthusen H, Lipfert P, Zeilhofer HU (2004) The spinal antinociceptive effect of nocistatin in neuropathic rats is blocked by D-serine. Anesthesiology 101:753–758PubMedGoogle Scholar
  134. Nabekura J, Xu TL, Rhee JS, Li JS, Akaike N (1999) Alpha2-adrenoceptor-mediated enhancement of glycine response in rat sacral dorsal commissural neurons. Neuroscience 9:29–41Google Scholar
  135. Nagy GG, Al-Ayyan M, Andrew D, Fukaya M, Watanabe M, Todd AJ (2004) Widespread expression of the AMPA receptor GluR2 subunit at glutamatergic synapses in the rat spinal cord and phosphorylation of GluR1 in response to noxious stimulation revealed with an antigen-unmasking method. J Neurosci 24:5766–5777PubMedGoogle Scholar
  136. Narikawa K, Furue H, Kumamoto E, Yoshimura M (2000) In vivo patch-clamp analysis of IPSCs evoked in rat substantia gelatinosa neurons by cutaneous mechanical stimulation. J Neurophysiol 84:2171–2174PubMedGoogle Scholar
  137. Narumiya S, Sugimoto Y, Ushikubi F (1999) Prostanoid receptors: structures, properties, and functions. Physiol Rev 79:1193–1226PubMedGoogle Scholar
  138. Nebe J, Vanegas H, Neugebauer V, Schaible HG (1997) ω-agatoxin IVA, a P-type calcium channel antagonist, reduces nociceptive processing in spinal cord neurons with input from the inflamed but not from the normal knee joint—an electrophysiological study in the rat in vivo. Eur J Neurosci 9:2193–2201PubMedGoogle Scholar
  139. Nichols ML, Allen BJ, Rogers SD, Ghilardi JR, Honore P, Luger NM, Finke MP, Li J, Lappi DA, Simone DA, Mantyh PW (1999) Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science 286:1558–1561PubMedGoogle Scholar
  140. Okuda-Ashitaka E, Minami T, Tachibana S, Yoshihara Y, Nishiuchi Y, Kimura T, Ito S (1998) Nocistatin, a peptide that blocks nociceptin action in pain transmission. Nature 392:286–289PubMedGoogle Scholar
  141. Pan YZ, Li DP, Pan HL (2002) Inhibition of glutamatergic synaptic input to spinal lamina IIo neurons by presynaptic α2-adrenergic receptors. J Neurophysiol 87:1938–1947PubMedGoogle Scholar
  142. Patel S, Naeem S, Kesingland A, Froestl W, Capogna M, Urban L, Fox A (2001) The effects of GABA(B) agonists and gabapentin on mechanical hyperalgesia in models of neuropathic and inflammatory pain in the rat. Pain 90:217–226PubMedGoogle Scholar
  143. Polgar E, Hughes DI, Riddell JS, Maxwell DJ, Puskar Z, Todd AJ (2003) Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain. Pain 104:229–239PubMedGoogle Scholar
  144. Polgar E, Gray S, Riddell JS, Todd AJ (2004) Lack of evidence for significant neuronal loss in laminae I-III of the spinal dorsal horn of the rat in the chronic constriction injury model. Pain 111:144–150PubMedGoogle Scholar
  145. Popratiloff A, Weinberg RJ, Rustioni A (1996) AMPA receptor subunits underlying terminals of fine-caliber primary afferent fibers. J Neurosci 16:3363–3372PubMedGoogle Scholar
  146. Qian J, Brown SD, Carlton SM (1996) Systemic ketamine attenuates nociceptive behaviors in a rat model of peripheral neuropathy. Brain Res 715:51–62PubMedGoogle Scholar
  147. Randic M, Jiang MC, Cerne R (1993) Long-term potentiation and long-term depression of primary afferent neurotransmission in the rat spinal cord. J Neurosci 13:5228–5241PubMedGoogle Scholar
  148. Rees H, Sluka KA, Westlund KN, Willis WD (1995) The role of glutamate and GABA receptors in the generation of dorsal root reflexes by acute arthritis in the anaesthetized rat. J Physiol 484:437–445PubMedGoogle Scholar
  149. Reinold H, Ahmadi S, Depner UB, Layh B, Heindl C, Hamza M, Pahl A, Brune K, Narumiya S, Müller U, Zeilhofer HU (2005) Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype. J Clin Invest 115:673–679PubMedGoogle Scholar
  150. 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 270:792–794PubMedGoogle Scholar
  151. Rhee JS, Wang ZM, Nabekura J, Inoue K, Akaike N (2000) ATP facilitates spontaneous glycinergic IPSC frequency at dissociated rat dorsal horn interneuron synapses. J Physiol 524:471–483PubMedGoogle Scholar
  152. Roche KW, O’Brien RJ, Mammen AL, Bernhardt J, Huganir RL (1996) Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. Neuron 16:1179–1188PubMedGoogle Scholar
  153. Rudolph U, Möhler H (2004) Analysis of GABAA receptor function and dissection of the pharmacology of benzodiazepines and general anesthetics through mouse genetics. Annu Rev Pharmacol Toxicol 44:475–498PubMedGoogle Scholar
  154. Ruscheweyh R, Sandkühler J (2002) Role of kainate receptors in nociception. Brain Res Brain Res Rev 40:215–222PubMedGoogle Scholar
  155. Saegusa H, Kurihara T, Zong S, Minowa O, Kazuno A, Han W, Matsuda Y, Yamanaka H, Osanai M, Noda T, Tanabe T (2000) Altered pain responses in mice lacking alpha 1E subunit of the voltage-dependent Ca2+ channel. Proc Natl Acad Sci USA 97:6132–6137PubMedGoogle Scholar
  156. Saegusa H, Kurihara T, Zong S, Kazuno A, Matsuda Y, Nonaka T, Han W, Toriyama H, Tanabe T (2001) Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel. EMBO J 20:2349–2356PubMedGoogle Scholar
  157. Salio C, Fischer J, Franzoni MF, Mackie K, Kaneko T, Conrath M (2001) CB1-cannabinoid and mu-opioid receptor co-localization on postsynaptic target in the rat dorsal horn. Neuroreport 12:3689–3692PubMedGoogle Scholar
  158. Samad TA, Moore KA, Sapirstein A, Billet S, Allchorne A, Poole S, Bonventre JV, Woolf CJ (2001) Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 410:471–475PubMedGoogle Scholar
  159. Sandkühler J (2000) Learning and memory in pain pathways. Pain 88:113–118PubMedGoogle Scholar
  160. Sandkühler J, Liu X (1998) Induction of long-term potentiation at spinal synapses by noxious stimulation or nerve injury. Eur J Neurosci 10:2476–2480PubMedGoogle Scholar
  161. Sandkühler J, Chen JG, Cheng G, Randic M (1997) Low-frequency stimulation of afferent Aδ-fibers induces long-term depression at primary afferent synapses with substantia gelatinosa neurons in the rat. J Neurosci 17:6483–6491PubMedGoogle Scholar
  162. Schneider SP, Eckert WA III, Light AR (1998) Opioid-activated postsynaptic, inward rectifying potassium currents in whole cell recordings in substantia gelatinosa neurons. J Neurophysiol 80:2954–2962PubMedGoogle Scholar
  163. Schroeder JE, McCleskey EW (1993) Inhibition of Ca2+ currents by a μ-opioid in a defined subset of rat sensory neurons. J Neurosci 13:867–873PubMedGoogle Scholar
  164. Schuler V, Luscher C, Blanchet C, Klix N, Sansig G, Klebs K, Schmutz M, Heid J, Gentry C, Urban L, Fox A, Spooren W, Jaton AL, Vigouret J, Pozza M, Kelly PH, Mosbacher J, Froestl W, Kaslin E, Korn R, Bischoff S, Kaupmann K, van der Putten H, Bettler B (2001) Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABAB responses in mice lacking GABAB1. Neuron 31:47–58PubMedGoogle Scholar
  165. Schulte G, Robertson B, Fredholm BB, DeLander GE, Shortland P, Molander C (2003) Distribution of antinociceptive adenosine A1 receptors in the spinal cord dorsal horn, and relationship to primary afferents and neuronal subpopulations. Neuroscience 121:907–916PubMedGoogle Scholar
  166. Seeburg PH, Higuchi M, Sprengel R (1998) RNA editing of brain glutamate receptor channels: mechanism and physiology. Brain Res Brain Res Rev 26:217–229PubMedGoogle Scholar
  167. Seltzer Z, Devor M (1979) Ephaptic transmission in chronically damaged peripheral nerves. Neurology 29:1061–1064PubMedGoogle Scholar
  168. Sheen K, Chung JM (1993) Signs of neuropathic pain depend on signals from injured nerve fibers in a rat model. Brain Res 610:62–68PubMedGoogle Scholar
  169. Shimoyama M, Shimoyama N, Hori Y (2000) Gabapentin affects glutamatergic neurotransmission in the rat dorsal horn. Pain 85:405–414PubMedGoogle Scholar
  170. Sivilotti L, Woolf CJ (1994) The contribution of GABAA and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord. J Neurophysiol 72:169–179PubMedGoogle Scholar
  171. Sommer C (2003) Painful neuropathies. Curr Opin Neurol 16:623–628PubMedGoogle Scholar
  172. Sorkin LS, Yaksh TL, Doom CM (1999) Mechanical allodynia in rats is blocked by a Ca2+ permeable AMPA receptor antagonist. Neuroreport 10:3523–3526PubMedGoogle Scholar
  173. Stanfa LC, Hampton DW, Dickenson AH (2000) Role of Ca2+-permeable non-NMDA glutamate receptors in spinal nociceptive transmission. Neuroreport 11:3199–3202PubMedGoogle Scholar
  174. Szekely JI, Torok K, Mate G (2002) The role of ionotropic glutamate receptors in nociception with special regard to the AMPA binding sites. Curr Pharm Des 8:887–912PubMedGoogle Scholar
  175. Tachibana M, Wenthold RJ, Morioka H, Petralia RS (1994) Light and electron microscopic immunocytochemical localization of AMPA-selective glutamate receptors in the rat spinal cord. J Comp Neurol 344:431–454PubMedGoogle Scholar
  176. Taddese A, Nah SY, McCleskey EW (1995) Selective opioid inhibition of small nociceptive neurons. Science 270:1366–1369PubMedGoogle Scholar
  177. Takeda D, Nakatsuka T, Papke R, Gu JG (2003) Modulation of inhibitory synaptic activity by a non-α4β2, non-α7 subtype of nicotinic receptors in the substantia gelatinosa of adult rat spinal cord. Pain 101:13–23PubMedGoogle Scholar
  178. Tatsuo MA, Salgado JV, Yokoro CM, Duarte ID, Francischi JN (1999) Midazolam-induced hyperalgesia in rats: modulation via GABAA receptors at supraspinal level. Eur J Pharmacol 370:9–15PubMedGoogle Scholar
  179. Taylor CP (2004) The biology and pharmacology of calcium channel alpha2-delta proteins. CNS Drug Rev 10:183–188PubMedGoogle Scholar
  180. Tognetto M, Amadesi S, Harrison S, Creminon C, Trevisani M, Carreras M, Matera M, Geppetti P, Bianchi A (2001) Anandamide excites central terminals of dorsal root ganglion neurons via vanilloid receptor-1 activation. J Neurosci 21:1104–1109PubMedGoogle Scholar
  181. Travagli RA, Williams JT (1996) Endogenous monoamines inhibit glutamate transmission in the spinal trigeminal nucleus of the guinea-pig. J Physiol 491:177–185PubMedGoogle Scholar
  182. Vanegas H, Schaible HG (2001) Prostaglandins and cyclooxygenases in the spinal cord. Prog Neurobiol 64:327–363PubMedGoogle Scholar
  183. Vasquez E, Bär KJ, Ebersberger A, Klein B, Vanegas H, Schaible HG (2001) Spinal prostaglandins are involved in the development but not the maintenance of inflammation-induced spinal hyperexcitability. J Neurosci 21:9001–9008PubMedGoogle Scholar
  184. 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 534:849–859PubMedGoogle Scholar
  185. Wall PD, Woolf CJ (1984) Muscle but not cutaneous C-afferent input produces prolonged increases in the excitability of the flexion reflex in the rat. J Physiol 356:443–458PubMedGoogle Scholar
  186. Westergren I, Nystrom B, Hamberger A, Nordborg C, Johansson BB (1994) Concentrations of amino acids in extracellular fluid after opening of the blood-brain barrier by intracarotid infusion of protamine sulfate. J Neurochem 62:159–165PubMedGoogle Scholar
  187. Willis WD Jr (1999) Dorsal root potentials and dorsal root reflexes: a double-edged sword. Exp Brain Res 124:395–421PubMedGoogle Scholar
  188. Xu TL, Nabekura J, Akaike N (1996) Protein kinase C-mediated enhancement of glycine response in rat sacral dorsal commissural neurones by serotonin. J Physiol 496:491–501PubMedGoogle Scholar
  189. Xu TL, Pang ZP, Li JS, Akaike N (1998) 5-HT potentiation of the GABAA response in the rat sacral dorsal commissural neurones. Br J Pharmacol 124:779–787PubMedGoogle Scholar
  190. Yang K, Fujita T, Kumamoto E (2004) Adenosine inhibits GABAergic and glycinergic transmission in adult rat substantia gelatinosa neurons. J Neurophysiol 92:2867–2877PubMedGoogle Scholar
  191. Zamanillo D, Sprengel R, Hvalby O, Jensen V, Burnashev N, Rozov A, Kaiser KM, Köster HJ, Borchardt T, Worley P, Lübke J, Frotscher M, Kelly PH, Sommer B, Andersen P, Seeburg PH, Sakmann B (1999) Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning. Science 284:1805–1811PubMedGoogle Scholar
  192. Zeilhofer HU (2005) The glycinergic control of nociception. Cell Mol Life Sci (in press; Jun 17 Epub ahead of print)Google Scholar
  193. Zeilhofer HU, Calò G (2003) Nociceptin/orphanin FQ and its receptor-potential targets for pain therapy? J Pharmacol Exp Ther 306:423–429PubMedGoogle Scholar
  194. Zeilhofer HU, Muth-Selbach U, Gühring H, Erb K, Ahmadi S (2000) Selective suppression of inhibitory synaptic transmission by nocistatin in the rat spinal cord dorsal horn. J Neurosci 20:4922–4999PubMedGoogle Scholar
  195. Zou X, Lin Q, Willis WD (2002) Role of protein kinase A in phosphorylation of NMDA receptor 1 subunits in dorsal horn and spinothalamic tract neurons after intradermal injection of capsaicin in rats. Neuroscience 115:775–786PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Institut für Pharmakologie und ToxikologieUniversität ZürichZürichSwitzerland

Personalised recommendations