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The role of excitatory amino acid receptors and intracellular messengers in persistent nociception after tissue injury in rats

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Abstract

Increased pain sensitivity (hyperalgesia) and persistent nociception following peripheral tissue injury depends both on an increase in the sensitivity of primary afferent nociceptors at the site of injury (peripheral sensitization), and on an increase in the excitability of neurons in the central nervous system (central sensitization). We will review evidence that central sensitization, and the persistent nociception it leads to, are dependent on an action of glutamate and aspartate at excitatory amino acid (EAA) receptors. Additional evidence will be presented implicating a role of various intracellular second messengers that are coupled to EAA receptors (nitric oxide, arachidonic acid, and protein kinase C) to central sensitization and persistent nociception following tissue injury. Finally, we will examine the evidence for a contribution of molecular events, including noxious stimulus-induced expression of immediate-early genes such as c-fos to persistent nociception.

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References

  • Aanonsen L. M., Lei S., and Wilcox G. L. (1990) Excitatory amino acid receptors and nociceptive neuro-transmission in rat spinal cord.Pain 41, 309–321.

    Article  PubMed  CAS  Google Scholar 

  • Aanonsen L. M. and Wilcox G. L. (1986) Phencyclidine selectively blocks a spinal action of N-methyl-d-aspartate in mice.Neurosci. Lett. 67, 191–197.

    Article  PubMed  CAS  Google Scholar 

  • Aanonsen L. M. and Wilcox G. L. (1987) Nociceptive action of excitatory amino acids in the mouse: effects of spinally administered opioids phencyclidine and σ agonists.J. Pharmacol. Exp. Ther. 243, 9–19.

    PubMed  CAS  Google Scholar 

  • Alkon D. L., Kubota M., Neary J. T., Naito S., Coulter D., and Rasmussen H. (1986) C-Kinase activation prolongs Ca2+-dependent inactivation of K+ channels.Biochem. Biophys. Res. Commun. 134, 1245–1253.

    Article  PubMed  CAS  Google Scholar 

  • Anikstejn L., Bregestovski P., and Ben-Ari Y. (1991) Selective activation of quisqualate metabotropic receptor potentiates NMDA but not AMPA responses.Eur. J. Pharmacol. 205, 327–328.

    Article  Google Scholar 

  • Ben-Ari Y., Aniksztejn L., and Bregestovski P. (1992) Protein kinase C modulation of NMDA currents: an important link for LTP induction.TINS 15, 333–339.

    PubMed  CAS  Google Scholar 

  • Ben-Sreti M. M., Gonzalez J. P., and Sewell R. D. E. (1983) Effects of elevated calcium and calcium antagonists on 6,7-benzomorphan-induced analgesia.Eur. J. Pharmacol. 90, 385–391.

    Article  PubMed  CAS  Google Scholar 

  • Benedek G. and Szikszay M. (1984) Potentiation of thermoregulatory and analgesic effects of morphine by calcium antagonists.Pharmacol. Res. Commun. 16, 1009–1017.

    Article  PubMed  CAS  Google Scholar 

  • Berridge M. J. and Galione A. (1988) Cytsolic calcium oscillators.FASEB J. 2, 3074–3083.

    PubMed  CAS  Google Scholar 

  • Birder L. A. and deGroat W. C. (1992) The effect of glutamate antagonists on c-fos expression induced in spinal neurons by irritation of the lower urinary tract.Brain Res. 580, 115–120.

    Article  PubMed  CAS  Google Scholar 

  • Chapman D. B. and Way E. L. (1982) Modification of endorphin/enkephalin analgesia and stress-induced analgesia by divalent cations, a cation chelator, and an ionophore.Br. J. Pharmacol. 75, 389–396.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Chi S. I., Levine J. D., and Basbaum A. I. (1990) Time course of peripheral neuroma-induced expression of Fos protein immunoreactivity in the spinal cord of rats and effects of local anesthetics.Soc. Neurosci. Abstr. 16, 566.

    Google Scholar 

  • Contreras E., Tamayo L., and Amigo M. (1988) Calcium channel antagonists increase morphine-induced analgesia and antagonize morphine tolerance.Eur. J. Pharmacol. 148, 463–466.

    Article  PubMed  CAS  Google Scholar 

  • Coderre T. J. and Melzack R. (1991) Central neural mediators of secondary hyperalgesia following heat injury in rats: neuropeptides and excitatory amino acids.Neurosci. Lett. 131, 71–74.

    Article  PubMed  CAS  Google Scholar 

  • Coderre T. J. and Melzack R. (1992a) The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury.J. Neurosci. 12, 3665–3670.

    PubMed  CAS  Google Scholar 

  • Coderre T. J. and Melzack R. (1992b) The role of NMDA receptor-operated calcium channels in persistent nociception after formalin-induced tissue injury.J. Neurosci. 12, 3671–3675.

    PubMed  CAS  Google Scholar 

  • Coderre T. J., Vaccarino A. L., and Melzack R. (1990) Central nervous system plasticity in the tonic pain response to subcutaneous formalin injection.Brain Res. 535, 155–158.

    Article  PubMed  CAS  Google Scholar 

  • Coderre T. J., Katz J., Vaccarino A. L., and Melzack R. (1993) Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence.Pain 53, 1–27.

    Article  Google Scholar 

  • Curtis D. R. and Watkins J. C. (1960) The excitation and depression of spinal neurons by structurally-related amino acids.J. Neurochem. 6, 117–141.

    Article  PubMed  CAS  Google Scholar 

  • Davar G., Hama A., Deykin A., Vos B., and Maciewicz R. (1991) MK-801 blocks the development of thermal hyperalgesia in a rat model of experimental painful neuropathy.Brain Res. 553, 327–330.

    Article  PubMed  CAS  Google Scholar 

  • Davies J. and Watkins J. C. (1983) Role of excitatory amino acid receptors in mono- and polysynaptic excitation in cat spinal cord.Exp. Brain Res. 49, 280–290.

    Article  PubMed  CAS  Google Scholar 

  • Davies S. N. and Lodge D. (1987) Evidence for involvement of N-methylaspartate receptors in “wind-up” of class 2 neurones in the dorsal horn of the rat.Brain Res. 424, 402–406.

    Article  PubMed  CAS  Google Scholar 

  • Dawson V. L., Dawson T. M., London E. D., Bredt D. S., and Synder S. H. (1991) Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures.Proc. Natl. Acad. Sci. USA 88, 6368–6371.

    Article  PubMed  CAS  Google Scholar 

  • DeBiasi S. and Rustioni A. (1988) Glutamate and substance P coexist in primary afferent terminals in the superficial laminae of spinal cord.Proc. Natl. Acad. Sci. USA 85, 7820–7824.

    Article  CAS  Google Scholar 

  • DeRiemer S. A., Strong J. A., Albert K. A., Greengard P., and Kaczmarek L. K. (1985) Enhancement of calcium current inAplysia by phorbol ester and protein kinase C.Nature 313, 313–316.

    Article  PubMed  CAS  Google Scholar 

  • Del Pozo E., Caro G., and Baeyens J. M. (1987) Analgesic effects of several calcium channel blockers in mice.Eur. J. Pharmacol. 137, 155–160.

    Article  PubMed  Google Scholar 

  • Dickenson A. H. and Sullivan A. F. (1987) Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deep rat dorsal horn nociceptive neurones following C fibre stimulation.Neuropharmacology 26, 1235–1238.

    Article  PubMed  CAS  Google Scholar 

  • Doerner B. and Alger B. E. (1988) Cyclic GMP depresses hippocampal Ca2+ current through a mechanism independent of cGMP-dependent protein kinase.Neuron 1, 693–699.

    Article  PubMed  CAS  Google Scholar 

  • Dougherty P. M. and Willis W. D. (1991a) Modification of the responses of primate spinothalamic neurons to mechanical stimulation by excitatory amino acids and anN-methyl-D-aspartate antagonist.Brain Res. 542, 15–22.

    Article  PubMed  CAS  Google Scholar 

  • Dougherty P. M. and Willis W. D. (1991b) Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined microiontophoretic application of N-methyl-D-aspartic acid and substance P.Pain 47, 85–93.

    Article  PubMed  CAS  Google Scholar 

  • Dougherty P. M. and Willis W. D. (1992) Enhanced responses of spinothalamic tract neurons to excitatory amino acids accompany capsaicin-induced sensitization in the monkey.J. Neurosci. 12, 883–894.

    PubMed  CAS  Google Scholar 

  • Dougherty P. M., Palecek J., Paleckova V., Sorkin L. S., and Willis W. D. (1992) The role of NMDA and non-NMDA excitatory amino acid receptors in the excitation of primate spinothalamic tract neurons by mechanical thermal and electrical stimuli.J. Neurosci. 12, 3025–3041.

    PubMed  CAS  Google Scholar 

  • Dubner R. and Ruda M. A. (1992) Activity-dependent neuronal plasticity following tissue injury and inflammation.Trends Neurosci. 15, 96–103.

    Article  PubMed  CAS  Google Scholar 

  • Dumuis A., Sebben M., Haynes L., Pin J.-P., and Bockaert J. (1988) NMDA receptors activate the arachidonic acid cascade system in striatal neurons.Nature 336, 68–70.

    Article  PubMed  CAS  Google Scholar 

  • Dumuis A., Pin J.-P., Oomagari K., Sebben M., and Bockaert J. (1990) Arachidonic acid released from striatal neurons by joint stimulation of ionotropic and metabotropic quisqualate receptors.Nature 347, 182–184.

    Article  PubMed  CAS  Google Scholar 

  • Eaton S. A. and Salt T. E. (1990) Thalamic NMDA receptors and nociceptive sensory synaptic transmission,Neurosci. Lett. 110, 297–302.

    Article  PubMed  CAS  Google Scholar 

  • Gammon C. M., Allen A. C. C., and Morell P. (1989) Bradykinin stimulates phosphoinositide hydrolysis and mobilization of arachidonic acid in dorsal root ganglion neurons.J. Neurochem. 53, 95–101.

    Article  PubMed  CAS  Google Scholar 

  • Garthwaite J., Charles S. L., and Chess-Williams R. (1988) Endothelium-derived relaxing factors released on activation of NMDA receptors suggests role a intracellular messenger in the brain.Nature 336, 385–388.

    Article  PubMed  CAS  Google Scholar 

  • Gerber G., Kangrga I., Ryu P. D., Larew J. S. A., and Randic M. (1989) Multiple effects of phorbol esters in the rat spinal dorsal horn.J. Neurosci. 9, 3606–3617.

    PubMed  CAS  Google Scholar 

  • Gerber G. and Randic M. (1989) Participation of excitatory amino acid receptors in the slow excitatory synaptic transmission in the rat spinal cord in vitro.Neurosci. Lett. 106, 220–228.

    Article  PubMed  CAS  Google Scholar 

  • Haley J. E., Sullivan A. F., and Dickenson A. H. (1990) Evidence for spinal N-methyl-D-aspartate receptor involvement in prolonged chemical nociception in the rat.Brain Res. 518, 218–226.

    Article  PubMed  CAS  Google Scholar 

  • Haley J. E., Dickenson A. H., and Schachter M. (1992a) Electrophysiological evidence for a role of nitric oxide in prolonged chemical nociception in rat.Neuropharmacology 31, 251–258.

    Article  PubMed  CAS  Google Scholar 

  • Haley J. E., Wilcox G. L. and Chapman P. F. (1992b) The role of nitric oxide in hippocampal long-term potentiation.Neuron 8, 211–216.

    Article  PubMed  CAS  Google Scholar 

  • Hargreaves K., Dubner R., Brown F., Flores C., and Joris J. (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.Pain 32, 77–88.

    Article  PubMed  CAS  Google Scholar 

  • Harris R. A., Loh H. H., and Way E. L. (1975) Effects of divalent cations, cation chelators, and an ionophore on morphine analgesia and tolerance.J. Pharmacol. Exp. Ther. 195, 488–498.

    PubMed  CAS  Google Scholar 

  • Hayes R. L., Mao J., Price D. D., Germano A., D'Avella D., Fiori M., and Mayer D. L. (1992) Pretreatment with gangliosides reduces abnormal nociceptive responses associated with a rodent mononeuropathy.Pain 48, 391–396.

    Article  PubMed  CAS  Google Scholar 

  • Herdegen T., Leah J. D., Walter T., Basler B., and Zimmermann M. (1990a) Activated neurons in CNS pathways detected via early and protooncogene protein products.Pain (Suppl.)5, S97.

    Article  Google Scholar 

  • Herdegen T., Walker T., Leah J. D., Bravo R., and Zimmermann M. (1990b) The KROX-24 protein, a new transcription regulating factor: expression in the rat central nervous system following afferent somatosensory stimulation.Neurosci. Lett. 120, 21–24.

    Article  PubMed  CAS  Google Scholar 

  • Herdegen T., Leah J. D., Manisali A., Bravo R., and Zimmermann M. (1991a).c-jun-like immunoreactivity in the CNS of the adult rat: basal and trans-synaptically induced expression of an immediate-early gene.Neuroscience 41, 643–654.

    Article  PubMed  CAS  Google Scholar 

  • Herdegen T., Leah J. D., Walter T., Basler B., Bravo R., and Zimmermann M. (1991b) Noxious stimulation induces molecular genetic events in neurons of the central nervous system: expression of immediate-early gene encoded proteins, inPain Research and Clinical Management, vol. 4,Proceedings of the VIth World Congress on Pain (Bond M. R., Charlton J. E., and Woolf C. J., eds.), Elsevier, Amsterdam, pp. 325–330.

    Google Scholar 

  • Herdegen T., Tolle T. R., Bravo R., Zieglgänsberger W., and Zimmermann M. (1991c) Sequential expression of Jun B, Jun D, and Fos B proteins in rat spinal neurons: cascade of transcriptional operations during nociception.Neurosci. Lett. 129, 221–224.

    Article  PubMed  CAS  Google Scholar 

  • Hisanaga K., Sagar S. M., and Sharp F. R. (1992) N-methyl-D-aspartate antagonists block Fos-like protein expression induced via multiple signaling pathways in cultured cortical neurons.J. Neurochem. 58, 1836–1844.

    Article  PubMed  CAS  Google Scholar 

  • Hu G.-Y., Hvalby O., Walaas S. I., Albert K. A., Skjeflo P., Andersen P., and Greengard P. (1987) Protein kinase C injection into hippocampal pyramidal cells elicits features of long term potentiation.Nature 328, 426–429.

    Article  PubMed  CAS  Google Scholar 

  • Iadorola M. J., Douglass J., Civelli O., and Naranjo J. R. (1988) Differential activation of spinal cord dynorphin and enkephalin neurons during hyperalgesia: evidence using cDNA hybridization.Brain Res. 455, 205–212.

    Article  CAS  Google Scholar 

  • Kangrga I. and Randic M. (1990) Tachykinins and calcitonin gene-related peptide enhance release of endogenous glutamate and aspartate from the rat spinal dorsal horn slice.J. Neurosci. 10, 2026–2038.

    PubMed  CAS  Google Scholar 

  • Kelso S. R., Nelson T. E., and Leonard J. P. (1992) Protein kinase C-mediated enhancement of NMDA currents by metabotropic glutamate receptors in xenopus oocytes.J. Physiol. 449, 705–718.

    PubMed  CAS  Google Scholar 

  • Kim D. and Clapham D. E. (1989) Potassium channels in cardiac cells activated by arachidonic acid and phospholipids.Science 224, 1174–1176.

    Article  Google Scholar 

  • King A. E., Thompson S. W. N., Urban L., and Woolf C. J. (1988) An intracellular analysis of amino acid induced excitations of deep dorsal horn neurones in the rat spinal cord slice.Neurosci. Lett. 89, 286–292.

    Article  PubMed  CAS  Google Scholar 

  • Kurachi Y., Ito H., Sugimoto T., Shimizu T., Miki I., and Ui M. (1989) Arachidonic acid metabolites as intracellular modulators of G protein-gated cardiac K+ channels.Nature 337, 555–557.

    Article  PubMed  CAS  Google Scholar 

  • Lerea L. S., Bulter L. S., and McNamara J. O. (1992) NMDA and non-NMDA receptor-mediated increase of c-fos mRNA in dentate gyrus neurons involves calcium influx via different routes.J. Neurosci. 12, 2973–2981.

    PubMed  CAS  Google Scholar 

  • MacDermott A. B., Mayer M. L., Westbrook G. L., Smith S. J., and Barker J. L. (1986) NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurons.Nature 321, 519–522.

    Article  PubMed  CAS  Google Scholar 

  • Madison D. V., Malenka R. C., and Nicoll R. A. (1986) Phorbol esters block a voltage-sensitive chloride current in hippocampal cells.Nature 321, 695–697.

    Article  PubMed  CAS  Google Scholar 

  • Malenka R. C., Madison D. V., and Nicoll R. A. (1986) Potentiation of synaptic transmission in the hippocampus by phorbol esters.Nature 321, 175–177.

    Article  PubMed  CAS  Google Scholar 

  • Malmberg A. B. and Yaksh T. L. (1992a) Antinociceptive actions of spinal nonsteroidal antiinflammatory agents on the formalin test in the rat.J. Pharmacol. Exp. Ther. 263, 136–146.

    PubMed  CAS  Google Scholar 

  • Malmberg A. B. and Yaksh T. L. (1992b) Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition.Science 257, 1276–1279.

    Article  PubMed  CAS  Google Scholar 

  • Manzoni O. J. J., Finiels-Marlier F., Sassetti I., Blockaert J., lePench C., and Sladeczek F. A. J. (1990) The glutamate receptor of the Qp-type activates protein kinase C and is regulated by protein kinase C.Neurosci. Lett. 109, 146–151.

    Article  PubMed  CAS  Google Scholar 

  • Mao J., Price D. D., Mayer D. J., Lu J., and Hayes R. L. (1992) Intrathecal MK801 and local nerve anesthesia synergistically reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy.Brain Res. 576, 252–262.

    Article  Google Scholar 

  • Maurset A., Skoglund L. A., Hustveit O., and Oye I. (1989) Comparison of ketamine and pethidine in experimental and postoperative pain.Pain 36, 37–41.

    Article  PubMed  CAS  Google Scholar 

  • Mayer M. L., Westbrook G. L., and Guthrie P. B. (1984) Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones.Nature 309, 261–263.

    Article  PubMed  CAS  Google Scholar 

  • Mayer M. L. and Miller R. J. (1991) Excitatory amino acid receptors second messengers and regulation of intracellular Ca2+ in mammalian neurons, inThe Pharmacology of Excitatory Amino Acids A, TIPS Special Report (Lodge D. and Collingridge G. L., eds.), Elsevier, Cambridge, UK, pp. 36–42.

    Google Scholar 

  • Meller S. T., Dykstra C., and Gebhart G. H. (1992a) Production of endogenous nitric oxide and activation of soluble guanylate cyclase are required for N-methyl-D-aspartate-produced facilitation of the nociceptive tail-flick reflex.Eur. J. Pharmacol 214, 93–96.

    Article  PubMed  CAS  Google Scholar 

  • Meller S. T., Pechman P. S., Gebhart G. F., and Maues T. J. (1992b) Nitric oxide mediates the thermal hyperalgesia produced in a model of neuropathic pain in the rat.Neuroscience 50, 7–10.

    Article  PubMed  CAS  Google Scholar 

  • Miranda H. F., Bustamante D., Kramer V., Pelisser T., Saavedra H., Paeile C., Fernandez E., and Pinardi G. (1992) Antinociceptive effects of Ca2+ channel blockers.Eur. J. Pharmacol. 217, 137–141.

    Article  PubMed  CAS  Google Scholar 

  • Mjellen-Joly N., Lund A., Berge O.-G., and Hole K. (1992) Intrathecal coadministration of substance P and NMDA augments nociceptive responses in the formalin test.Pain 51, 195–198.

    Article  Google Scholar 

  • Moore P. K., Oluyomi A. O., Babbedge R. C., Wallace P., and Hart S. L. (1991) L-N6-nitro arginine methyl ester exhibits antinociceptive activity in the mouse.Br. J. Pharmacol. 102, 198–202.

    PubMed  CAS  Google Scholar 

  • Morgan J. I. and Curran T. (1986) Role of ion flux in the control of c-fos expression.Nature 322, 552–555.

    Article  PubMed  CAS  Google Scholar 

  • Morgan J. I. and Curran T. (1991) Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenesfos andjun.Ann. Rev. Neurosci. 14, 421–451.

    Article  PubMed  CAS  Google Scholar 

  • Murphy S. N. and Miller R. J. (1988) Regulation of Ca2+ influx into striatal neurons by kainic acid.Proc. Natl. Acad. Sci. USA 85, 8737–8741.

    Article  PubMed  CAS  Google Scholar 

  • Murphy S. N. and Miller R. J. (1989) Regulation of Ca2+ influx into striatal neurons by kainic acid.J. Pharmacol. Exp. Ther. 249, 184–193.

    PubMed  CAS  Google Scholar 

  • Naranjo J. R., Mellstrom B., Achaval M., and Sassone-Corsi P. (1991) Molecular pathways of pain: Fos/Jun-mediated activation of a noncanonical AP-1 site in the prodynorphin gene.Neuron 6, 607–617.

    Article  PubMed  CAS  Google Scholar 

  • Nestler E. J. and Greengard P. (1983) Protein phosphorylation in the brain.Nature (Lond.) 305, 583–588.

    Article  CAS  Google Scholar 

  • Nishizuka Y. (1986) Studies and perspectives of protein kinase C.Science 233, 305–312.

    Article  PubMed  CAS  Google Scholar 

  • Noguchi K., Kowalski K., Traub R., Solodkin A., Iadorola M. J. and Ruda M. A. (1991) Dynorphin expression and Fos-like immunoreactivity following inflammation induced hyperalgesia are colocalized in spinal cord neurons.Mol. Brain Res. 10, 227–233.

    Article  PubMed  CAS  Google Scholar 

  • Noguchi K., Dubner R., and Ruda M. A. (1992) Preproenkephalin mRNA in spinal dorsal horn neurons is induced by peripheral inflammation and is colocalized with Fos and Fos-related proteins.Neuroscience 46, 561–570.

    Article  PubMed  CAS  Google Scholar 

  • Nowak L., Bregestovski P., Ascher P., Hebert A., and Prochiantz A. (1984) Magnesium gates glutamateactivated channels in mouse central neurones.Nature 307, 462–465.

    Article  PubMed  CAS  Google Scholar 

  • Randic M., Hecimoviec H., and Ryu P. D. (1990) Substance P modulates glutamate-induced currents in aceutyly isolated rat spinal dorsal horn neurones.Neurosci. Lett. 117, 74–80.

    Article  PubMed  CAS  Google Scholar 

  • Rasmussen H. (1986) The calcium messenger system.N. Engl. J. Med. 314, 1094–1101.

    Article  PubMed  CAS  Google Scholar 

  • Ren K., Hylden J. L. K., Williams G. M., Ruda M. A., and Dubner R. (1991) Effects of MK-801 on behavioral hyperalgesia and dorsal horn neuronal activity in rats with adjuvant-induced inflammation.Soc. Neurosci. Abtr. 17, 1208.

    Google Scholar 

  • Schaible H.-G., Grubb B. D., Neugebauer V., and Oppmann M. (1991) The effects of NMDA antagonists on neuronal activity in cat spinal cord evoked by acute inflammation in the knee joint.Eur. J. Neurosci. 3, 981–991.

    Article  PubMed  Google Scholar 

  • Schneider S. P. and Perl E. R. (1988) Comparison of primary afferent and glutamate excitation of neurons in mammalian spinal cord dorsal horn.J. Neurosci. 8, 2062–2073.

    PubMed  CAS  Google Scholar 

  • Seltzer Z., Cohn S., Ginzburg R., and Beilin B. Z. (1991) Modulation of neuropathic pain behavior in rats by spinal disinhibition and NMDA receptor blockade of injury discharge.Pain 45, 69–75.

    Article  PubMed  CAS  Google Scholar 

  • Sher G. and Mitchell D. (1990) N-methyl-D-aspartate receptors mediate responses of rat dorsal horn neurons to hindlimb ischemia.Brain Res. 522, 55–62.

    Article  PubMed  CAS  Google Scholar 

  • Skilling S. R., Smullin D. H., and Larson A. A. (1988) Extracellular amino acid concentrations in the dorsal spinal cord of freely moving rats following veratridine and nociceptive stimulation.J. Neurochem. 51, 127–132.

    Article  PubMed  CAS  Google Scholar 

  • Skilling S. R., Harkness D. H., and Larson A. A. (1992) Experimental peripheral neuropathy decreases the dose of substance P required to increase excitatory amino acid release in the CSF of rat spinal cord.Neurosci. Lett. 135, 92–96.

    Article  Google Scholar 

  • Sladeczek F., Pin J.-P., Recasens M., Bockaert J., and Weiss S. (1985) Glutamate stimulates inositol phosphate formation in striatal neurons.Nature 317, 717–719.

    Article  PubMed  CAS  Google Scholar 

  • Smullin D. H., Skilling S. R., and Larson A. A. (1990) Interaction between substance P calcitonin gene related peptide taurine and excitatory amino acids in the spinal cord.Pain 42, 93–101.

    Article  PubMed  CAS  Google Scholar 

  • Southam E., East S. J., and Garthwaite J. (1991) Excitatory amino acid receptors coupled to the nitric oxide: cyclic GMP pathway in rat cerebellum during development.J. Neurochem. 56, 2072–2081.

    Article  PubMed  CAS  Google Scholar 

  • Sugiyama H., Ito I., and Hirono C. (1987) A new type of glutamate receptor linked to inositol phospholipid metabolism.Nature 325, 531–533.

    Article  PubMed  CAS  Google Scholar 

  • Synder S. H. (1992) Nitric oxide: first in a new class of neurotransmitters.Science 257, 494–496.

    Article  Google Scholar 

  • Szekely A. M., Barbaccia M. L., and Costa E. (1987) Activation of specific glutamate receptor subtypes increases c-fos proto-oncogene expression in primary cultures of neonatal rat cerebellar granule cells.Neuropharmacology 26, 1779–1782.

    Article  PubMed  CAS  Google Scholar 

  • Szekely A. M., Barbaccia M. L., Alho H., and Costa E. (1989) In primary cultures of cerebellar granule cells the activation of N-methyl-D-aspartatesensitive glutamate receptors induces c-fos mRNA expression.Mol. Pharmacol. 35, 401–408.

    PubMed  CAS  Google Scholar 

  • Thompson S. W. N., King A. E., and Woolf C. J. (1990) Activity-dependent changes in rat ventral horn neuronesin vitro; summation of prolonged afferent evoked postsynaptic depolarizations produce a d-APV sensitive windup.Eur. J. Neurosci. 2, 638–649.

    Article  PubMed  CAS  Google Scholar 

  • Tolle T. R., Castro-Lopes J. M., Evan G., and Zieglgänsberger W. (1991) 1 C-fos induction in the spinal cord following noxious stimulation: prevention by opiates but not by NMDA antagonists, inPain Research and Clinical Management, vol. 4,Proceedings of the VIth World Congress on Pain (Bond M. R., Charlton J. E., and Woolf C. J., eds.), Elsevier, Amsterdam, pp. 299–305.

    Google Scholar 

  • Vaccarino F., Guidotti A., and Costa E. (1987) Ganglioside inhibition of glutamate-mediated protein kinase C translocation in primary cultures of cerebellar neurons.Proc. Natl. Acad. Sci. USA 84, 8707–8711.

    Article  PubMed  CAS  Google Scholar 

  • Vaccarino A. L., Marek P., Kest B., Weber E., and Liebeskind J. C. (1992) Noncompetitive NMDA antagonist MK-801, and glycine antagonist ACEA-1011, prevent the development of tonic pain following sc formalin.Soc. Neurosci. Abstr. 18, 686.

    Google Scholar 

  • Watkins J. C. and Evans R. H. (1981) Excitatory amino acid transmitters.Ann. Rev. Pharmacol. Toxicol. 21, 165–204.

    Article  CAS  Google Scholar 

  • Willcockson W. S., Chung, J. M., Hori Y., Lee K. H., and Willis W. D. (1984a) Effects of iontophorectically released amino acids and amines on primate spinothalamic tract cells.J. Neurosci. 4, 732–740.

    PubMed  CAS  Google Scholar 

  • Willcockson W. S., Chung J. M., Hori Y., Lee K. H., and Willis W. D. (1984b) Effects of iontophorectically released peptides on primates spinothalamic tract cells.J. Neurosci. 4, 741–750.

    PubMed  CAS  Google Scholar 

  • Williams J. H., Errington M. L., Lynch M. A., and Bliss T. V. P. (1990a) Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus.Nature 341, 739–742.

    Article  Google Scholar 

  • Williams S., Evan G. I., and Hunt S. P. (1990b) Changing patterns of c-fos induction in spinal neurons following thermal cutaneous stimulation in the rat.Neuroscience 36, 73–81.

    Article  PubMed  CAS  Google Scholar 

  • Wisden W., Errinton M. L., Williams S., Dunnett S. B., Waters C., Hitchcock D., Evan G., Bliss T. V. P., and Hunt S. P. (1990) Differential expression of immediate early genes in the hippocampus and spinal cord.Neuron 4, 603–614.

    Article  PubMed  CAS  Google Scholar 

  • Woolf C. J. and Wiesenfeld-Hallin Z. (1986) Substance P and calcitonin generelated peptide synergistically modulate the gain of the nociceptive flex or withdrawal reflex in the rat.Neurosci. Lett. 66, 226–230.

    Article  PubMed  CAS  Google Scholar 

  • Woolf C. J. and Thompson S. W. N. (1991) The induction and maintenance of central sensitization is dependent on N-methyl-d-aspartic acid receptor activation: implications for post-injury pain hypersensitivity states.Pain 44, 293–299.

    Article  PubMed  CAS  Google Scholar 

  • Woolf C. J. (1991) Central mechanisms of acute pain, inPain Research and Clinical Management, vol. 4,Proceedings of the VIth World Congress on Pain (Bond M. R., Charlton J. E., and Woolf C. J., eds.), Elsevier, Amsterdam, pp. 25–34.

    Google Scholar 

  • Yaksh T. C. (1982) Central and peripheral mechanisms for the antialgesic acition of acetylsalicylic acid, inAcetylsalicylic Acid: New Uses for an Old Drug (Barett H. J. M., Hirsh J., and Mustard J. F., eds.), Raven, New York, pp. 137–151.

    Google Scholar 

  • Yashpal K. and Coderre T.J. (1993) Contribution of nitric oxide arachidonic acid and protein kinase C to persistent pain following tissue injury in rats. Abstracts of the Seventh World Congress on Pain, p. 24.

  • Yamamoto T. and Yaksh T. L. (1992) Comparison of the antinociceptive effects of pre- and posttreatment with intrathecal morphine and MK-801, an NMDA antagonist on the formalin test in the rat.Anaesthesiology 77, 757–763.

    Article  CAS  Google Scholar 

  • Zieglgänsberger W. and Herz A. (1971) Chanaes of cutaneous receptive field of spinocervical tract neurons and other dorsal horn neurons by microelectrophorectically administered amino acids.Exp. Brain Res. 13, 111–126.

    Article  PubMed  Google Scholar 

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Coderre, T.J. The role of excitatory amino acid receptors and intracellular messengers in persistent nociception after tissue injury in rats. Mol Neurobiol 7, 229–246 (1993). https://doi.org/10.1007/BF02769177

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