Skip to main content

Synaptic modulation in pain pathways

  • Chapter
  • First Online:
Book cover Reviews of Physiology, Biochemistry and Pharmacology

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

Abstract

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.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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 59:612–618

    PubMed  CAS  Google Scholar 

  • Ahmadi S, Lippross S, Neuhuber WL, Zeilhofer HU (2002) PGE2 selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons. Nat Neurosci 5:34–40

    PubMed  CAS  Google Scholar 

  • 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 300:2094–2097

    PubMed  CAS  Google Scholar 

  • 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 11:2758–2766

    PubMed  CAS  Google Scholar 

  • 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 73:509–518

    PubMed  CAS  Google Scholar 

  • 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 86:273–282

    PubMed  CAS  Google Scholar 

  • 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 106:373–379

    PubMed  CAS  Google Scholar 

  • 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 83:955–962

    PubMed  CAS  Google Scholar 

  • 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 92:485–492

    PubMed  CAS  Google Scholar 

  • 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 92:473–484

    PubMed  CAS  Google Scholar 

  • Baba H, Kohno T, Moore KA, Woolf CJ (2001) Direct activation of rat spinal dorsal horn neurons by prostaglandin E2. J Neurosci 21:1750–1756

    PubMed  CAS  Google Scholar 

  • 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 24:642–651

    PubMed  Google Scholar 

  • 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 17:5297–5304

    PubMed  CAS  Google Scholar 

  • 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 24:2774–2781

    PubMed  CAS  Google Scholar 

  • 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 276:2042–2045

    PubMed  CAS  Google Scholar 

  • Basbaum AI, Fields HL (1984) Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 7:309–338

    PubMed  CAS  Google Scholar 

  • 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 46:743–749

    PubMed  CAS  Google Scholar 

  • 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 390:165–169

    PubMed  CAS  Google Scholar 

  • Bennett MI, Simpson KH (2004) Gabapentin in the treatment of neuropathic pain. Palliat Med 18:5–11

    PubMed  Google Scholar 

  • Berger AJ, Dieudonne S, Ascher P (1998) Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J Neurophysiol 80:3336–3340

    PubMed  CAS  Google Scholar 

  • 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 95:15730–15734

    PubMed  CAS  Google Scholar 

  • 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 279:1243–1249

    PubMed  CAS  Google Scholar 

  • Breitinger HG, Becker CM (1998) The inhibitory glycine receptor: prospects for a therapeutic orphan? Curr Pharm Des 4:315–334

    PubMed  CAS  Google Scholar 

  • 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 124:891–900

    PubMed  CAS  Google Scholar 

  • Brown JT, Randall A (2005) Gabapentin fails to alter P/Q-type Ca2+ channel-mediated synaptic transmission in the hippocampus. Synapse 55:262–269

    PubMed  CAS  Google Scholar 

  • Cervero F, Laird JM (1996) Mechanisms of allodynia: interactions between sensitive mechanoreceptors and nociceptors. Neuroreport 7:526–528

    PubMed  CAS  Google Scholar 

  • 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 39:2231–2243

    PubMed  CAS  Google Scholar 

  • Chen L, Huang LY (1992) Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation. Nature 356:521–523

    PubMed  CAS  Google Scholar 

  • 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 19:7342–7355

    PubMed  CAS  Google Scholar 

  • 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 84:1006–1011

    PubMed  CAS  Google Scholar 

  • Chizh BA, Headley PM, Tzschentke TM (2001) NMDA receptor antagonists as analgesics: focus on the NR2B subtype. Trends Pharmacol Sci 22:636–642

    PubMed  CAS  Google Scholar 

  • 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 404:95–106

    PubMed  CAS  Google Scholar 

  • 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 325:151–153

    PubMed  CAS  Google Scholar 

  • Cordero-Erausquin M, Changeux JP (2001) Tonic nicotinic modulation of serotoninergic transmission in the spinal cord. Proc Natl Acad Sci USA 98:2803–2807

    PubMed  CAS  Google Scholar 

  • Cordero-Erausquin M, Pons S, Faure P, Changeux JP (2004) Nicotine differentially activates inhibitory and excitatory neurons in the dorsal spinal cord. Pain 109:308–318

    PubMed  CAS  Google Scholar 

  • 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 424:938–942

    PubMed  CAS  Google Scholar 

  • 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 17:2381–2387

    PubMed  Google Scholar 

  • 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 96:3269–3274

    PubMed  CAS  Google Scholar 

  • 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 45:171–190

    PubMed  CAS  Google Scholar 

  • Durand GM, Kovalchuk Y, Konnerth A (1996) Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381:71–75

    PubMed  CAS  Google Scholar 

  • 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 19:2081–2089

    PubMed  CAS  Google Scholar 

  • 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 8:1967–1970

    PubMed  CAS  Google Scholar 

  • 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 6:136–143

    PubMed  CAS  Google Scholar 

  • 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 122:237–245

    PubMed  CAS  Google Scholar 

  • 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 130:900–906

    PubMed  CAS  Google Scholar 

  • 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 42:229–236

    PubMed  CAS  Google Scholar 

  • Flores CM (2000) The promise and pitfalls of a nicotinic cholinergic approach to pain management. Pain 88:1–6

    PubMed  CAS  Google Scholar 

  • 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 373:79–84

    PubMed  CAS  Google Scholar 

  • 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 112:315–323

    PubMed  CAS  Google Scholar 

  • Garraway SM, Hochman S (2001) Serotonin increases the incidence of primary afferent-evoked long-term depression in rat deep dorsal horn neurons. J Neurophysiol 85:1864–1872

    PubMed  CAS  Google Scholar 

  • 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 24:6086–6097

    PubMed  CAS  Google Scholar 

  • 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 24:797–807

    PubMed  CAS  Google Scholar 

  • Goodchild CS, Serrao JM (1987) Intrathecal midazolam in the rat: evidence for spinally-mediated analgesia. Br J Anaesth 59:1563–1570

    PubMed  CAS  Google Scholar 

  • Grisel JE, Mogil JS, Belknap JK, Grandy DK (1996) Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide. Neuroreport 7:2125–2129

    PubMed  CAS  Google Scholar 

  • 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 507:473–483

    PubMed  CAS  Google Scholar 

  • Gu JG, MacDermott AB (1997) Activation of ATP P2X receptors elicits glutamate release from sensory neuron synapses. Nature 389:749–753

    PubMed  CAS  Google Scholar 

  • Gu JG, Albuquerque C, Lee CJ, MacDermott AB (1996) Synaptic strengthening through activation of Ca2+-permeable AMPA receptors. Nature 381:793–796

    PubMed  CAS  Google Scholar 

  • Gu Y, Huang LY (2002) Gabapentin potentiates N-methyl-D-aspartate receptor mediated currents at GABAergic dorsal horn neurons. Neurosci Lett 324:177–180

    PubMed  CAS  Google Scholar 

  • 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 279:24866–24872

    PubMed  CAS  Google Scholar 

  • 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 24:9161–9173

    PubMed  CAS  Google Scholar 

  • Harris J, Drew LJ, Chapman V (2000) Spinal anandamide inhibits nociceptive transmission via cannabinoid receptor activation in vivo. Neuroreport 11:2817–2819

    PubMed  CAS  Google Scholar 

  • 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 44:637–650

    PubMed  CAS  Google Scholar 

  • 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 304:884–887

    PubMed  CAS  Google Scholar 

  • Hebb DO (1966) A textbook of psychology. Saunders, Philadelphia

    Google Scholar 

  • 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 492:867–876

    PubMed  CAS  Google Scholar 

  • Hugel S, Schlichter R (2000) Presynaptic P2X receptors facilitate inhibitory GABAergic transmission between cultured rat spinal cord dorsal horn neurons. J Neurosci 20:2121–2130

    PubMed  CAS  Google Scholar 

  • Hugel S, Schlichter R (2003) Convergent control of synaptic GABA release from rat dorsal horn neurones by adenosine and GABA autoreceptors. J Physiol 551:479–489

    PubMed  CAS  Google Scholar 

  • 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 122:1339–1344

    PubMed  CAS  Google Scholar 

  • 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 436:275–289

    PubMed  CAS  Google Scholar 

  • Ikeda H, Heinke B, Ruschewey R, Sandkühler J (2003) Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science 299:1237–1240

    PubMed  CAS  Google Scholar 

  • 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 85:385–393

    PubMed  CAS  Google Scholar 

  • 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 536:505–519

    PubMed  CAS  Google Scholar 

  • Jasmin L, Wu MV, Ohara PT (2004) GABA puts a stop to pain. Curr Drug Targets CNS Neurol Disord 3:487–505

    PubMed  CAS  Google Scholar 

  • Ji RR, Kohno T, Moore KA, Woolf CJ (2003) Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 26:696–705

    PubMed  CAS  Google Scholar 

  • Jo YH, Schlichter R (1999) Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosci 2:241–245

    PubMed  CAS  Google Scholar 

  • Johnson JW, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325:529–531

    PubMed  CAS  Google Scholar 

  • 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 86:348–354

    PubMed  CAS  Google Scholar 

  • Kable JW, Murrin LC, Bylund DB (2000) In vivo gene modification elucidates subtype-specific functions of α2-adrenergic receptors. J Pharmacol Exp Ther 293:1–7

    PubMed  CAS  Google Scholar 

  • 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 279:33684–33695

    PubMed  CAS  Google Scholar 

  • 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 292:743–751

    PubMed  CAS  Google Scholar 

  • 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 98:682–689

    PubMed  CAS  Google Scholar 

  • 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 21:7871–7880

    PubMed  CAS  Google Scholar 

  • Kelly S, Chapman V (2001) Selective cannabinoid CB1 receptor activation inhibits spinal nociceptive transmission in vivo. J Neurophysiol 86:3061–3064

    PubMed  CAS  Google Scholar 

  • 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 32:477–488

    PubMed  CAS  Google Scholar 

  • Kerchner GA, Wilding TJ, Li P, Zhuo M, Huettner JE (2001b) Presynaptic kainate receptors regulate spinal sensory transmission. J Neurosci 21:59–66

    PubMed  CAS  Google Scholar 

  • 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 127:843–852

    PubMed  CAS  Google Scholar 

  • 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 22:9086–9098

    PubMed  CAS  Google Scholar 

  • Kiyosawa A, Katsurabayashi S, Akaike N, Pang ZP, Akaike N (2001) Nicotine facilitates glycine release in the rat spinal dorsal horn. J Physiol 536:101–110

    PubMed  CAS  Google Scholar 

  • Kleckner NW, Dingledine R (1988) Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes. Science 241:835–837

    PubMed  CAS  Google Scholar 

  • 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 24:964–971

    PubMed  CAS  Google Scholar 

  • Klugbauer N, Marais E, Hofmann F (2003) Calcium channel α2δ subunits: differential expression, function, and drug binding. J Bioenerg Biomembranes 35:639–647

    CAS  Google Scholar 

  • 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 518:803–813

    Google Scholar 

  • 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 68:1573–1580

    PubMed  CAS  Google Scholar 

  • 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 94:9950–9955

    PubMed  CAS  Google Scholar 

  • 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 125:221–231

    PubMed  CAS  Google Scholar 

  • 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 23:519–527

    PubMed  CAS  Google Scholar 

  • 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 10:1537–1541

    PubMed  CAS  Google Scholar 

  • Legendre P (2001) The glycinergic inhibitory synapse. Cell Mol Life Sci 58:760–793

    PubMed  CAS  Google Scholar 

  • 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 52:559–565

    PubMed  CAS  Google Scholar 

  • Li P, Zhuo M (1998) Silent glutamatergic synapses and nociception in mammalian spinal cord. Nature 393:695–698

    PubMed  CAS  Google Scholar 

  • 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 80:3356–3360

    PubMed  CAS  Google Scholar 

  • Li P, Wilding TJ, Kim SJ, Calejesan AA, Huettner JE, Zhuo M (1999) Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord. Nature 397:161–164

    PubMed  CAS  Google Scholar 

  • 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 121:425–432

    PubMed  CAS  Google Scholar 

  • 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 82:3316–3326

    PubMed  CAS  Google Scholar 

  • 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 191:43–46

    PubMed  CAS  Google Scholar 

  • 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 91:8383–8387

    PubMed  CAS  Google Scholar 

  • Liu H, Mantyh PW, Basbaum AI (1997) NMDA-receptor regulation of substance P release from primary afferent nociceptors. Nature 386:721–724

    PubMed  CAS  Google Scholar 

  • 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 10:3069–3075

    PubMed  CAS  Google Scholar 

  • 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 290:131–134

    PubMed  Google Scholar 

  • Lu CR, Hwang SJ, Phend KD, Rustioni A, Valtschanoff JG (2002) Primary afferent terminals in spinal cord express presynaptic AMPA receptors. J Neurosci 22:9522–9529

    PubMed  CAS  Google Scholar 

  • 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 21:1868–1875

    PubMed  CAS  Google Scholar 

  • 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 109:349–358

    PubMed  CAS  Google Scholar 

  • 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 303:1199–1205

    PubMed  CAS  Google Scholar 

  • Lynch JW (2004) Molecular structure and function of the glycine receptor chloride channel. Physiol Rev 84:1051–1095

    PubMed  CAS  Google Scholar 

  • 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 292:2501–2504

    PubMed  CAS  Google Scholar 

  • 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 17:7462–7470

    PubMed  CAS  Google Scholar 

  • 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 278:275–279

    PubMed  CAS  Google Scholar 

  • Mao J, Chen LL (2000) Gabapentin in pain management. Anesth Analg 91:680–687

    PubMed  CAS  Google Scholar 

  • Marais E, Klugbauer N, Hofmann F (2001) Calcium channel α2δ subunits-structure and gabapentin binding. Mol Pharmacol 59:1243–1248

    PubMed  CAS  Google Scholar 

  • 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 383:819–823

    PubMed  CAS  Google Scholar 

  • 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 3:587–592

    PubMed  CAS  Google Scholar 

  • Meder WP, Dooley DJ (2000) Modulation of K+-induced synaptosomal calcium influx by gabapentin. Brain Res 875:157–159

    PubMed  CAS  Google Scholar 

  • Mendell LM (1966) Physiological properties of unmyelinated fiber projections to the spinal cord. Exp Neurol 16:316–332

    PubMed  CAS  Google Scholar 

  • 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 377:532–535

    PubMed  CAS  Google Scholar 

  • Miljanich GP (2004) Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Curr Med Chem 11:3029–3040

    PubMed  CAS  Google Scholar 

  • 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 11:1849–1856

    PubMed  CAS  Google Scholar 

  • 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 100:271–276

    PubMed  CAS  Google Scholar 

  • 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 341:33–38

    PubMed  CAS  Google Scholar 

  • Moore KA, Baba H, Woolf CJ (2002a) Gabapentin-actions on adult superficial dorsal horn neurons. Neuropharmacology 43:1077–1081

    PubMed  CAS  Google Scholar 

  • 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 22:6724–6731

    PubMed  CAS  Google Scholar 

  • Morisset V, Urban L (2001) Cannabinoid-induced presynaptic inhibition of glutamatergic EPSCs in substantia gelatinosa neurons of the rat spinal cord. J Neurophysiol 86:40–48

    PubMed  CAS  Google Scholar 

  • 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 277:40342–44051

    PubMed  CAS  Google Scholar 

  • 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 101:753–758

    PubMed  CAS  Google Scholar 

  • 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 9:29–41

    Google Scholar 

  • 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 24:5766–5777

    PubMed  CAS  Google Scholar 

  • 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 84:2171–2174

    PubMed  CAS  Google Scholar 

  • Narumiya S, Sugimoto Y, Ushikubi F (1999) Prostanoid receptors: structures, properties, and functions. Physiol Rev 79:1193–1226

    PubMed  CAS  Google Scholar 

  • 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 9:2193–2201

    PubMed  CAS  Google Scholar 

  • 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 286:1558–1561

    PubMed  CAS  Google Scholar 

  • 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 392:286–289

    PubMed  CAS  Google Scholar 

  • Pan YZ, Li DP, Pan HL (2002) Inhibition of glutamatergic synaptic input to spinal lamina IIo neurons by presynaptic α2-adrenergic receptors. J Neurophysiol 87:1938–1947

    PubMed  CAS  Google Scholar 

  • 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 90:217–226

    PubMed  CAS  Google Scholar 

  • 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 104:229–239

    PubMed  CAS  Google Scholar 

  • 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 111:144–150

    PubMed  CAS  Google Scholar 

  • Popratiloff A, Weinberg RJ, Rustioni A (1996) AMPA receptor subunits underlying terminals of fine-caliber primary afferent fibers. J Neurosci 16:3363–3372

    PubMed  CAS  Google Scholar 

  • Qian J, Brown SD, Carlton SM (1996) Systemic ketamine attenuates nociceptive behaviors in a rat model of peripheral neuropathy. Brain Res 715:51–62

    PubMed  CAS  Google Scholar 

  • 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 13:5228–5241

    PubMed  CAS  Google Scholar 

  • 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 484:437–445

    PubMed  CAS  Google Scholar 

  • 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 115:673–679

    PubMed  CAS  Google Scholar 

  • 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 270:792–794

    PubMed  CAS  Google Scholar 

  • 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 524:471–483

    PubMed  CAS  Google Scholar 

  • Roche KW, O’Brien RJ, Mammen AL, Bernhardt J, Huganir RL (1996) Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. Neuron 16:1179–1188

    PubMed  CAS  Google Scholar 

  • 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 44:475–498

    PubMed  CAS  Google Scholar 

  • Ruscheweyh R, Sandkühler J (2002) Role of kainate receptors in nociception. Brain Res Brain Res Rev 40:215–222

    PubMed  CAS  Google Scholar 

  • 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 97:6132–6137

    PubMed  CAS  Google Scholar 

  • 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 20:2349–2356

    PubMed  CAS  Google Scholar 

  • 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 12:3689–3692

    PubMed  CAS  Google Scholar 

  • 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 410:471–475

    PubMed  CAS  Google Scholar 

  • Sandkühler J (2000) Learning and memory in pain pathways. Pain 88:113–118

    PubMed  Google Scholar 

  • Sandkühler J, Liu X (1998) Induction of long-term potentiation at spinal synapses by noxious stimulation or nerve injury. Eur J Neurosci 10:2476–2480

    PubMed  Google Scholar 

  • 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 17:6483–6491

    PubMed  Google Scholar 

  • 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 80:2954–2962

    PubMed  CAS  Google Scholar 

  • Schroeder JE, McCleskey EW (1993) Inhibition of Ca2+ currents by a μ-opioid in a defined subset of rat sensory neurons. J Neurosci 13:867–873

    PubMed  CAS  Google Scholar 

  • 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 31:47–58

    PubMed  CAS  Google Scholar 

  • 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 121:907–916

    PubMed  CAS  Google Scholar 

  • Seeburg PH, Higuchi M, Sprengel R (1998) RNA editing of brain glutamate receptor channels: mechanism and physiology. Brain Res Brain Res Rev 26:217–229

    PubMed  CAS  Google Scholar 

  • Seltzer Z, Devor M (1979) Ephaptic transmission in chronically damaged peripheral nerves. Neurology 29:1061–1064

    PubMed  CAS  Google Scholar 

  • Sheen K, Chung JM (1993) Signs of neuropathic pain depend on signals from injured nerve fibers in a rat model. Brain Res 610:62–68

    PubMed  CAS  Google Scholar 

  • Shimoyama M, Shimoyama N, Hori Y (2000) Gabapentin affects glutamatergic neurotransmission in the rat dorsal horn. Pain 85:405–414

    PubMed  CAS  Google Scholar 

  • 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 72:169–179

    PubMed  CAS  Google Scholar 

  • Sommer C (2003) Painful neuropathies. Curr Opin Neurol 16:623–628

    PubMed  Google Scholar 

  • Sorkin LS, Yaksh TL, Doom CM (1999) Mechanical allodynia in rats is blocked by a Ca2+ permeable AMPA receptor antagonist. Neuroreport 10:3523–3526

    PubMed  CAS  Google Scholar 

  • Stanfa LC, Hampton DW, Dickenson AH (2000) Role of Ca2+-permeable non-NMDA glutamate receptors in spinal nociceptive transmission. Neuroreport 11:3199–3202

    PubMed  CAS  Google Scholar 

  • 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 8:887–912

    PubMed  CAS  Google Scholar 

  • 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 344:431–454

    PubMed  CAS  Google Scholar 

  • Taddese A, Nah SY, McCleskey EW (1995) Selective opioid inhibition of small nociceptive neurons. Science 270:1366–1369

    PubMed  CAS  Google Scholar 

  • 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 101:13–23

    PubMed  CAS  Google Scholar 

  • 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 370:9–15

    PubMed  CAS  Google Scholar 

  • Taylor CP (2004) The biology and pharmacology of calcium channel alpha2-delta proteins. CNS Drug Rev 10:183–188

    PubMed  Google Scholar 

  • 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 21:1104–1109

    PubMed  CAS  Google Scholar 

  • Travagli RA, Williams JT (1996) Endogenous monoamines inhibit glutamate transmission in the spinal trigeminal nucleus of the guinea-pig. J Physiol 491:177–185

    PubMed  CAS  Google Scholar 

  • Vanegas H, Schaible HG (2001) Prostaglandins and cyclooxygenases in the spinal cord. Prog Neurobiol 64:327–363

    PubMed  CAS  Google Scholar 

  • 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 21:9001–9008

    PubMed  CAS  Google Scholar 

  • 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 534:849–859

    PubMed  CAS  Google Scholar 

  • 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 356:443–458

    PubMed  CAS  Google Scholar 

  • 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 62:159–165

    PubMed  CAS  Google Scholar 

  • Willis WD Jr (1999) Dorsal root potentials and dorsal root reflexes: a double-edged sword. Exp Brain Res 124:395–421

    PubMed  CAS  Google Scholar 

  • 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 496:491–501

    PubMed  CAS  Google Scholar 

  • 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 124:779–787

    PubMed  CAS  Google Scholar 

  • Yang K, Fujita T, Kumamoto E (2004) Adenosine inhibits GABAergic and glycinergic transmission in adult rat substantia gelatinosa neurons. J Neurophysiol 92:2867–2877

    PubMed  CAS  Google Scholar 

  • 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 284:1805–1811

    PubMed  CAS  Google Scholar 

  • Zeilhofer HU (2005) The glycinergic control of nociception. Cell Mol Life Sci (in press; Jun 17 Epub ahead of print)

    Google Scholar 

  • Zeilhofer HU, Calò G (2003) Nociceptin/orphanin FQ and its receptor-potential targets for pain therapy? J Pharmacol Exp Ther 306:423–429

    PubMed  CAS  Google Scholar 

  • 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 20:4922–4999

    PubMed  CAS  Google Scholar 

  • 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 115:775–786

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hanns Ulrich Zeilhofer .

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag

About this chapter

Cite this chapter

Zeilhofer, H.U. (2005). Synaptic modulation in pain pathways. In: Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 154. Springer, Berlin, Heidelberg. https://doi.org/10.1007/s10254-005-0043-y

Download citation

Publish with us

Policies and ethics