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Neurochemical Research

, Volume 20, Issue 10, pp 1203–1210 | Cite as

The influence of glycine and related compounds on spinal cord injury-induced spasticity

  • Richard K. SimpsonJr.
  • Margaret Gondo
  • Claudia S. Robertson
  • J. Clay Goodman
Original Articles

Abstract

Spasticity is a frequent and complex sequel to spinal cord injury. The neurochemical basis for the origin of spasticity is largely unknown. Glycine is among the most abundant neurotransmitters in the spinal cord. However, the role of glycine and related compounds in spasticity have received little attention. An ischemic spinal cord injury was created in rabbits, by an intraaortic balloon occlusion technique, which produced lower limb spasticity. A catheter was inserted into the cisterna magna and the spinal cord was bathed with 100 μM solutions of glycine, strychnine,d-serine, β-alanine, MK-801, or artificial CSF for 4 hours at a rate of 10 μl/min. H-reflexes were monitored before and during infusion by stimulating the posterior tibial nerve and recording from the plantar surface of the foot. Glycine,d-serine, and MK-801 depressed the H wave, strychnine produced a heightened H wave, and β-alanine caused no significant changes. These results indicate that glycine and related compounds may influence spasticity.

Key Words

Intrathecal infusion glycine strychnine NMDA spasticity 

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References

  1. 1.
    Ashby, P., and McCrea, D. A. 1987. Neurophysiology of spasticity. Pages 119–143,in Davidoff, R. A., (ed), Handbook of the Spinal Cord, Congenital Disorders and Trauma, Marce Dekker, Inc, New York.Google Scholar
  2. 2.
    Howell, D. A., Lees, A. J., and Toghill, P. J. 1979. Spinal internuncial neurones in progressive encephalomyelitis with rigidity. J. Neurol. Neurosurg. Psychiatry 42:773–785.Google Scholar
  3. 3.
    Kupers, H. G. J. M. 1973. Pages 38–68,in Desmedt, J. E., (ed), New developments in electromyography and clinical neurophysiology, Basel, Karger.Google Scholar
  4. 4.
    Hall, P. V., Smith, J. E., Lane, J., Mote, T., and Campbell, R. 1979. Glycine and experimental spinal spasticity. Neurology 29:262–267.Google Scholar
  5. 5.
    Larson, A. A. 1989. Intrathecal GABA, glycine, taurine or beta-alanine elicits dyskinetic movements in mice. Pharmacol. Biochem. Behav. 32:505–509.Google Scholar
  6. 6.
    Smith, J. E., Hall, P. V., Galvin, M. R., Jones, A. R. and Campbell, R. L. 1979. Effects of glycine administration on canine experimental spinal spasticity and the levels of glycine, glutamate, and aspartate in the lumbar spinal cord. Neurosurgery 4:152–156.Google Scholar
  7. 7.
    Yaksh, T. L. 1989. Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: Effects of modulatory receptor systems and excitatory amino acid antagonists. Pain, 37:111–123.Google Scholar
  8. 8.
    Daly, E. C. and Aprison, M. H. 1983. Glycine. Pages 467–499,in Lajtha, A., (ed), Handbook of Neurochemistry, Plenum Press, New York.Google Scholar
  9. 9.
    Davidoff, R. A., Graham, L. T., Shank, R. P., Werman, R., and Aprison, M. H. 1967. Changes in amino acid concentrations associated with loss of spinal interneurons. J. Neurochem. 14:1025–1031.Google Scholar
  10. 10.
    Hammerstad, J. P., Murray, J. E., and Cutler, R. W. P. 1971. Efflux of amino acid neurotransmitters from rat spinal cord slices. II. Factors influencing the electrically induced efflux of [14C] glycine, and 3H-Gaba. Brain Res. 35:357–367.Google Scholar
  11. 11.
    Hopkin, J. and Neal, M. J. 1971. Effect of electrical stimulation and high potassium concentrations on the efflux of [14C] glycine from slices of spinal cord. Br. J. Pharmacol. 42:215–233.Google Scholar
  12. 12.
    Young, A. B. and Macdonald, R. L. 1987. Glycine as a spinal cord neurotransmitter. Pages 1–44,in Davidoff, R. A., (ed), Handbook of the Spinal Cord, Marcel Dekker Inc, New York.Google Scholar
  13. 13.
    Davidoff, R. A. 1985. Antispasticity drugs: Mechanism of action. Ann. Neurol. 17:107–116.Google Scholar
  14. 14.
    Herz, D. A., Looman, J. E., Tiberio, A., Ketterling, K., Kreitsch, R. K., Colwill, H. C., and Grin, O. D. 1990. The management of paralytic spasticity. Neurosurgery, 26:300–306.Google Scholar
  15. 15.
    Simpson, R. K. Jr., Robertson, C. S., and Goodman, J. C. 1993. Spinal epidural corticomotor evoked potentials as a predictor of outcome from ischemic myelopathy. Neurol. Res. 15:104–108.Google Scholar
  16. 16.
    Rymer, W. Z. and Powers, R. K. 1989. Pathophysiology of muscular hypertonia in spasticity. Pages 291–301,in Park, T. S., Phillips, L. H., and Peakock, W. J. (eds.), Management of spasticity interebral palsly and spinal cord injury, Neurosurgery: State of the Art Review, Hanley & Belfus, Inc., Philadelphia.Google Scholar
  17. 17.
    Shimoji, K., Shimizu, H., and Maruyama, Y. 1978. Origin of somatosensory evoked responses recorded from the cervical skin surface. J. Neurosurg. 48:980–984.Google Scholar
  18. 18.
    Ashby, P., Verrier, M., and Lightfoot, E. 1974. Segmental reflex pathways in spinal shock and spinal spasticity in man. J. Neurol. Neurosurg. Psychiat. 37:1352–1360.Google Scholar
  19. 19.
    Barolat-Romana, G. and Davis, R. 1980. Neurophysiological mechanisms in abnormal reflex activities in cerebral palsy and spinal spasticity. J. Neurol. Neurosurg. Psychiat. 43:333–342.Google Scholar
  20. 20.
    Fasano, V. A., Barolat-Romana, G., Zeme, S., and Sguazzi, L. 1979. Electrophysiological assessment of spinal circuits in spasticity by direct dorsal root stimulation. Neurosurgery, 4:146–151.Google Scholar
  21. 21.
    Lindsley, D. B., Schreiner, L. H., and Magoun, H. W. 1949. An electromyographic study of spasticity. J. Neurophysiol. 12:197–205.Google Scholar
  22. 22.
    Delwaide, P. J. 1985. Electrophysiological analysis of the mode of action of muscle relaxants in spasticity. Ann. Neurol. 17:90–95.Google Scholar
  23. 23.
    Dimitrijevic, M. M., Dimitrijevic, M. R., Sherwood, A. M., and Vanderlinden, C. 1989. Clinical neurophysiological techniques in the assessment of spasticity. Pages 64–83in Physical medicine and rehabilitation: State of the art reviews. Hanley & Belfus, Inc., Philadelphia.Google Scholar
  24. 24.
    Heller, A. H., and Hallett, M. 1982. Electrophysiological studies with the spastic mutant mouse. Brain Res. 234:299–308.Google Scholar
  25. 25.
    Meinck, H. M. 1976. Occurrence of the H reflex and the F wave in the rat. Electroencephalogr. Clin. Neurophysiol. 41:530–533.Google Scholar
  26. 26.
    Simpson, R. K. Jr., Robertson, C. S., and Goodman, J. C. 1989. Alterations in the corticomotor evoked potential following spinal cord ischemia. J Neurosci Meth, 28:171–178.Google Scholar
  27. 27.
    Simpson, R. K. Jr., Robertson, C. S., and Goodman, J. C. 1991. Segmental release of amino acid neurotransmitters from transcranial stimulation. Neurochem. Res. 16:89–94.Google Scholar
  28. 28.
    Simpson, R. K. Jr., Robertson, C. S., and Goodman, J. C. 1991. Release of segmental amino acid neurotransmitters in response to peripheral afferent and motor cortex stimulation: A pilot study. In Press, Life Sci (Pharm Lett), 49:113–118.Google Scholar
  29. 29.
    Simpson, R. K. Jr., Robertson, C. S., Goodman, J. C., and Halter, J. A. 1991. Recovery of amino acid neurotransmitters from the spinal cord during posterior epidural stimulation: A preliminary report. J. Am. Paraplegia Soc. 14:4–9.Google Scholar
  30. 30.
    Simpson, R. K. Jr., Robertson, C. S., and Goodman, J. C. 1993. Glycine: An important potential component of spinal shock. Neurochem. Res. 18:887–892.Google Scholar
  31. 31.
    Simpson, R. K. Jr., Robertson, C. S., and Goodman, J. C. 1993. Glycine: A potential mediator of electrically induced pain modification. Biomed. Lett. 48:193–207.Google Scholar
  32. 32.
    Simpson, R. K. Jr., Robertson, C. S., and Goodman, J. C. 1992. Segmental amino acid neurotransmitter recovery during posterior epidural stimulation after spinal cord injury. J. Am. Paraplegia Soc. 16:34–41.Google Scholar
  33. 33.
    Masland, R. 1985. Preface. Pages XV-XVI,in Eccles, J. and Dimitrijevic, M. R. (eds.), Recent Achievements in Restorative Neurology, Upper Motor Neuron Functions and Dysfunctions, Karger, Basel.Google Scholar
  34. 34.
    Park, T. S., Phillips, L. H., and Peakock, W. J. 1989. Preface. Pages xiii,in Park, T. S., Phillips, L. H., and Peakock, W. J., (eds.), Management of spasticity in cerebral palsly and spinal cord injury, Neurosurgery: State of the Art Review, Hanley & Belfus, Inc., Philadelphia.Google Scholar
  35. 35.
    Faganel, J. and Dimitrijevic, M. R. 1982. Study of propriospinal interneuron system in man. J Neurol Sci, 56:155–172.Google Scholar
  36. 36.
    Nathan, P. W. and Smith, M. C. 1959. Fasciculi proprii of the spinal cord in man. Review of present knowledge. Brain 82:610–668.Google Scholar
  37. 37.
    Neilson, P. D. 1972. Interaction between voluntary contraction and tonic stretch reflex transmission in normal and spastic patients. J. Neurol. Neurosurg. Psychiat. 35:853–860.Google Scholar
  38. 38.
    Shapovalov, A. I. 1975. Neuronal organization and synaptic mechanisms of supraspinal motor control in vertebrates. Rev. Physiol. Biochem. Pharmacol. 72:1–54.Google Scholar
  39. 39.
    Amassian, V. E., Stewart, B. S., Quirk, G. J., and Rosenthal, J. L. 1987. Physiological basis of motor effects of a transient stimulation to cerebral cortex, Neurosurgery 20:74–93.Google Scholar
  40. 40.
    Sherrington, C. S. and Sowton, S. C. M. 1915. Observations on reflex responses to single break shocks. J. Physiol. (London), 49:331–348.Google Scholar
  41. 41.
    Rizzoli, A. A. 1968. Distribution of glutamic acid, aspartic acid, g-aminobutyric acid and glycine in six areas of cat spinal cord before and after transection. Brain Res. 11:11–18.Google Scholar
  42. 42.
    Roberts, P. J., and Mitchell, J. F. 1972. The release of amino acids from the hemisected spinal cord during stimulation. J. Neurochem. 19:2473–2481.Google Scholar
  43. 43.
    Aprison, M. H. 1990. The discovery of the neurotransmitter role of glycine. Pages 1–23.in Ottersen, O. P. and Storm-Mathisen, J. (eds), Glycine Neurotransmission, John Wiley & Sons Ltd, New York.Google Scholar
  44. 44.
    Aprison, M. H., Shank, R. P., and Davidoff, R. A. 1969. A comparison of the concentration of glycine, a transmitter suspect, in different areas of the brain and spinal cord in seven different vertebrates. Comp. Biochem. Physiol. 28:1345–1355.Google Scholar
  45. 45.
    Christensen, H., Fykse, E. M., and Fonnum, F. 1990. Uptake of glycine into synaptic vesicles isolated from rat spinal cord. J. Neurochem. 54:1142–1147.Google Scholar
  46. 46.
    Kish, P. E., Fischer-Bovenkerk, C., and Ueda, T. 1989. Active transport of g-aminobutyric acid and glycine into synaptic vesicles. Proc. Natl. Acad. Sci. 86:3877–3881.Google Scholar
  47. 47.
    Berger, S. J., Carter, J. G., and Lowry, O. H. 1977. The distribution of glycine, GABA, glutamate, and aspartate in rabbit spinal cord, cerebellum and hippocampus. J. Neurochem. 28:149–158.Google Scholar
  48. 48.
    Fagg, G. E., Jordan, C. C., Webster, R. A. 1978. Descending fibre-mediated release of endogenous glutamate and glycine from the perfused cat spinal cord in vivo. Brain Res. 158:159–170.Google Scholar
  49. 49.
    Graham, L. T., Shank, R. P., Werman, R., and Aprison, M. H. 1967. Distribution of some synaptic transmitter suspects in cat spinal cord: glutamic acid, aspartic acid, g-aminobutyric acid, glycine, and glutamine. J. Neurochem. 14:465–472.Google Scholar
  50. 50.
    Ljungdahl, A., and Hokfelt, T. 1973. Accumulation of 3H-glycine in interneurons of the cat spinal cord. Histochemie, 33:277–280.Google Scholar
  51. 51.
    Davidoff, R. A. 1989. Mode of action of antispasticity drugs. Pages 315–324,in Park, T. S., Phillips, L. H., and Peakock, W. J., (eds.), Management of spasticity in cerebral palsly and spinal cord injury, Neurosurgery: State of the Art Review, Hanley & Belfus, Inc., Philadelphia.Google Scholar
  52. 52.
    Henneman, E. and Mendell, L. M. 1981. Functional organization of motorneuron pool and its inputs. Pages 423–507.in Brookhart, J. M. and Mountcastle, V. B., (eds.), The Nervous System, Handbook of Physiology, American Physiological Society, Bethesda.Google Scholar
  53. 53.
    Farrant, M., and Webster, R. A. 1989. Pages 161–219.in Boulton, A., Baker, G. B., and Juorio, A. V., (eds), Drugs as tools in neurotransmitter research. Humana Press Inc., Clifton.Google Scholar
  54. 54.
    Farrant, M., Gibbs, T. T., and Farb, D. H. 1990. Molecular and cellular mechanisms of GABA/Benzodiazepine-receptor regulation: Electrophysiological and biochemical studies. Neurochem. Res. 15:175–191.Google Scholar
  55. 55.
    Simpson, R. K. Jr., Robertson, C. S., and Goodman, J. C. 1990. Spinal cord ischemia-induced elevation of amino acids: Extracellular measurement with microdialysis. Neurochem. Res. 15:635–639.Google Scholar
  56. 56.
    Cahusac, P. M. B., Evans, R. H., Hill, R. G., Todriguez, R. E., and Smait, D. A. S. 1984. The behavioural effects of an N-methylaspartate receptor antagonist following application to the lumbar spinal cord of conscious rats. Neuropharmacology 23:719–724.Google Scholar
  57. 57.
    Gerber, G., Cerne, R., and Randic, M. 1991. Participation of excitatory amino acid receptors in the slow excitatory synaptic transmission in rat spinal dorsal horn. Brain Res. 561:236–251.Google Scholar
  58. 58.
    Hao, J. X., Xu, X. J., Aldskogius, H., Seiger, A., and Hallin Z. W. 1991. The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat. Exp. Neurol. 113:182–191.Google Scholar
  59. 59.
    Turski, L., Schwarz, M., Turski, W. A., Klockgether, T., Sontag, K. H., and Collins, J. F. 1985. Muscle relaxant action of excitatory amino acid antagonists. Neurosci. Lett. 53:321–326.Google Scholar
  60. 60.
    Chizhmakov, I. V., Kiskin, N. I., Krishtal, O. A., and Tsyndrenko, A. Y. 1989. Glycine action on N-methy-D-aspartate receptors in rat hippocampal neurons. Neurosci. Lett. 99:131–136.Google Scholar
  61. 61.
    McNamara, D., and Dingledine, R. 1990. Dual effect of glycine on NMDA-induced neurotoxicity in rat cortical cultures. J. Neurosci. 10:3970–3976.Google Scholar
  62. 62.
    Patel, J., Zinkland, W. C., Thompson, C., Keith, R., and Salama, A. 1990. Role of glycine in the N-methyl-D-aspartate-mediated neuronal cytotoxicity. J. Neurochem. 54:849–854.Google Scholar
  63. 63.
    Lester, R. A. J., Tong, G., and Jahr, C. E. 1993. Interactions between the glycine and glutamate binding sites of the NMDA receptor. J. Neurosci. 13:1088–1096.Google Scholar
  64. 64.
    Lynch, D. R., Anegawa, N. J., Verdoorn, T., and Pritchett, D. B. 1993. N-methyl-D-aspartate receptors: different subunit requirements for binding of glutamate antagonists, glycine antagonists, and channel-blocking agents. Molec Pharmacol, 45:540–545.Google Scholar
  65. 65.
    Van den Pol, A. N., and Gorcs, T. 1988. Glycine and glycine receptor immunoreactivity in brain and spinal cord. J Neurosci. 8:472–492.Google Scholar
  66. 66.
    Arizala, A. M., Rigamonti, D. D., Long, J. B., Kraimer, J. M., and Holaday, J. W. 1990. Effects of NMDA receptor antagonists following spinal ischemia in the rabbit. Exp. Neurol. 108:232–240.Google Scholar
  67. 67.
    Budai, D., Wilcox, G. L., and Larson, A. A. 1992. Enhancement of NMDA-evoked neuronal activity by glycine in the rat spinal cord in vivo. Neurosci. Lett. 135:265–268.Google Scholar
  68. 68.
    Douglas, J. R., Noga, B. R., Dai, X., and Jordan, L. M. 1993. The effects of intrathecal administration of excitatory amino acid agonists and antagonists on the initiation of locomotion in the adult cat. J. Neurosci., 13:990–1000.Google Scholar
  69. 69.
    Geyer, S. W., Gudden, W., Betz, H., Gnahn, H., and Weindl, A. 1987. Co-localization of choline acetyltransferase and postsynaptic glycine receptors in motoneurons of rat spinal cord demonstrated by immunocytochemistry: Neuroscience Lett. 82:11–15.Google Scholar
  70. 70.
    Bowker, R. M. and Abhold, R. H. 1990. Evoked changes in 5-hydroxytryptamine and norepinephrine release: in vivo dialysis of the rat dorsal horn. Eur. J. Pharmacol. 175:101–106.Google Scholar
  71. 71.
    Brodin, E., Linderoth, B., Gaselius, B., and Ungerstedt, U. 1987. In vivo release of substance P in cat dorsal horn studied with microdialysis. Neurosci. Lett. 76:357–362.Google Scholar
  72. 72.
    Pragg, H. V., and Frenk, H. 1990. The role of glutamate in opiate descending inhibition of nociceptive spinal reflexes. Brain Res. 524:101–105.Google Scholar
  73. 73.
    Schwarz, M., Klockgether, T., Wullner, U., Turski, L., and Sontag, K. H. 1988. d-aminovaleric acid antagonizes the pharmacological actions of baclofen in the central nervous system. Exp. Brain Res. 70:618–626.Google Scholar
  74. 74.
    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 the rat spinal cord. Neurosci. Lett. 139:92–96.Google Scholar
  75. 75.
    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.Google Scholar
  76. 76.
    Sorkin, L. S., Steinman, J. L., Hughes, M. G., Willis, W. D., and McAdoo, D. J. 1988. Microdialysis recovery of serotonin released in the spinal cord dorsal horn. J Neurosci Meth, 23:131–138.Google Scholar

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Richard K. SimpsonJr.
    • 1
  • Margaret Gondo
    • 1
  • Claudia S. Robertson
    • 1
  • J. Clay Goodman
    • 2
  1. 1.Department of NeurosurgeryBaylor College of MedicineHouston
  2. 2.Department of PathologyBaylor College of MedicineHouston

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