The role of glycine in pain and spasticity

  • R. K. SimpsonJr.
  • C. S. Robertson
  • J. Clay Goodman


Neuropathic pain is an intense pain perceived without an obvious noxious stimulus. Spasticity is heightened stretch reflexes and excessive muscle tonus. Both are a common and severely debilitating sequela to injury of the nervous system and both conditions frequently occur together simultaneously. In order to support this glycine-based theory we tested the primary hypothesis with the assumption that a relationship exists between segmentai glycine levels and neuropathic pain and spasticity. These tests included: 1) the detection of segmentai glycine release after motor and sensory pathway stimulation in normal injured animals, 2) the reduction of pain and spasticity following administration of glycine, and its receptor agonists, and 3) the production of pain and spasticity following administration of glycine receptor antagonists. Once fulfilled, results from these experiments would support the goal directed toward enhancing glycine receptor mechanisms as treatment for neuropathic pain and spasticity. Two animal models were employed to test the hypothesis, 1) a classic model of neuropathic pain in the rat created by sciatic nerve constriction, and 2) an established model of spasticity in the rabbit created by spinal cord ischemia.


Spinal Cord Neuropathic Pain Glycine Receptor Spinal Cord Ischemia Excitatory Amino Acid Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albright AL, Cervi A. Singletary J (1991) Intrathecal baclofen for spasticity in cerebral palsy. JAMA 265: 1418–1422PubMedCrossRefGoogle Scholar
  2. Amassian VE, Stewart BS, Quirk GJ, Rosenthal JL (1987) Physiological basis of motor effects of a transient stimulation to cerebral cortex. Neurosurgery 20: 74–93PubMedGoogle Scholar
  3. Aprison MH, Shank RP, Davidoff RA (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: 1345–1355PubMedCrossRefGoogle Scholar
  4. Aprison MH (1990) The discovery of the Neurotransmitter role of glycine. In: Ottersen OP, Storm-Mathisen J (eds) Glycine Neurotransmission. Wiley, New York, pp 1–23Google Scholar
  5. Araki T, Yamano M, Murakami T, Wanaka A, Betz H, Tohyama M (1988) Localization of glycine receptors in the rat central nervous system: An immunocytochemical analysis using monclonal antibody. Neuroscience 25: 613–624PubMedCrossRefGoogle Scholar
  6. Ashby P, Verrier M, Lightfoot E (1974) Segmentai reflex pathways in spinal shock and spinal spasticity in man. J Neurol Neurosurg Psychiatry 37: 1352–1360PubMedCrossRefGoogle Scholar
  7. Ashby P, McCrea DA (1987) Neurophysiology of spasticity. In: Davidoff RA (ed) Handbook of the Spinal Cord. Marcel Dekker, New York, pp 119–143Google Scholar
  8. Attal N, Jazat F, Kayser V, Guilbaud G (1990) Further evidence for pain related behaviours in a model of unilateral peripheral mononeuropathy. Pain 41: 235–251PubMedCrossRefGoogle Scholar
  9. Barbeau A (1974) Preliminary study of glycine administration in patients with spasticity. Neurology 24: 392Google Scholar
  10. Barolat-Romana G, Davis R (1980) Neurophysicological mechanisms in abnormal reflex activities in cerebral palsy and spinal spasticity. J Neurol Neurosurg Psychiatry 43: 333–342PubMedCrossRefGoogle Scholar
  11. Barolat G, Schwartzman RJ, Woo R (1989) Epidural spinal cord stimulation in the management of reflex syumpathetic dystrophy. Sterotac Funct Neurosurg 53: 29–39CrossRefGoogle Scholar
  12. Basbaum AI (1988) Distribution of glycine receptor immunoreactivity in the spinal cord of the rat: Cytochemical evidence for a differential glycinergic control of lamina I and V nociceptive neurons. J Comp Neurol 278: 330–336PubMedCrossRefGoogle Scholar
  13. Bennett GJ, Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33: 87–107PubMedCrossRefGoogle Scholar
  14. Bennett GJ, Kajander KC, Sahara Y (1989) Neurochemical and anatomical changes in the dorsal horn of rats with an experimental painful peripheral neuropathy. In: Cervero F, Bennett GJ, Headley PM (eds) The Superficial Dorsal Horn of the Spinal Cord. Plenum, New York, pp 463–471Google Scholar
  15. Bennett GJ (1991) Evidence from animai models on the pathogenesis of painful peripheral neuropathy: Relevance for pharmacotherapy. In: Basbaum AI, Beeson JM (eds) Toward a New Pharmacotherapy. Wiley, New York, pp 365–379Google Scholar
  16. Benveniste H, Hansen AJ, Ottosen NS (1989) Determination of brain interstitial concentrations by microdialysis. J Neuroehem 52: 1741–1750CrossRefGoogle Scholar
  17. Benveniste H (1989) Brain microdialysis: Short review. J Neurochem 52: 1667–1679PubMedCrossRefGoogle Scholar
  18. Berger SJ, Carter JG, Lowry OH (1977) The distribution of glycine, GABA, glutamate, and aspartate in rabbit spinal cord, cerebellum and hippocampus. J Neurochem 28: 149–158PubMedCrossRefGoogle Scholar
  19. Bernhard CG, Koll W (1953) On the effect of strychnine, asphyxia and dial on the spinal cord potentials. Acta Physiol Scand 29 [Suppl] 106: 30–41Google Scholar
  20. Beyer C, Banas C, Gomora P, Komisaruk BR (1988) Prevention of the convulsant and hyperalgesic action of strychnine by intrathecal glycine and related amino acids. Pharmacol Biochem Behav 29: 73–78PubMedCrossRefGoogle Scholar
  21. Beyer C, Banas C, Gonzalez-Flores O, Komisaruk BR (1989) Blockage of substance P-induced scratching behavior in rats by the intrathecal adminstration ofinhibitory amino acid agonists. Pharmacol Biochem Behav 34: 491–495PubMedCrossRefGoogle Scholar
  22. Bidlingmeyer BA, Cohen SA, Tarvin TL (1984) Rapid analysis of amino acids using pre-column derivatization. J Chromatogr 336: 93–104PubMedCrossRefGoogle Scholar
  23. Biscoe TJ, Duchen MR (1986) Synaptic physiology of spinal motoneurones of normal and spastic mice: an in vitro study. J Physiol 379: 275–292PubMedGoogle Scholar
  24. Boyd SG, Tothwell JC, Cowan MA, Webb PJ, Morley T, Asselman P, Marsden CD (1986) A method of monitoing function in corticospinal pathways during scoliosis surgery with a note on motor conduction velocities, j Neurol Neurosurg Psychiatry 49: 251–257PubMedCrossRefGoogle Scholar
  25. Brooks CM, Eccles JC (1947) A study of the effects of anaesthesia and asphyxia on the mono-synaptic pathway through the spinal cord. J Neurophysiol 10: 349–360PubMedGoogle Scholar
  26. Brown AC, Headly PM, West (1975) A device for producing reproducible electronically-timed pinch to provide noxious mechanical input. Proc Royal Soc 2: 123–125Google Scholar
  27. Bruggencate GT, Engberg I (1968) Analysis of glycine actions on spinal interneurones by intraceliular recording. Brain Res 11: 446–450PubMedCrossRefGoogle Scholar
  28. Brugger F, Wicki U, Elton DN, Fagg GE, Olpe HR, Pozza NM (1992) Modulation of the NMDA receptor by D-serine in the cortex and the spinal cord, in vitro. Europ J Pharmacol 191: 29–CrossRefGoogle Scholar
  29. Burke D, Ashby P (1972) Are spinal “presynaptic” inhibitory mechanisms supressed in spasticity? J Neurol Sci 15: 321–326PubMedCrossRefGoogle Scholar
  30. Cahusac PMB, Evans RH, Hill RG, Todriquez RE, Smait DAS (1984) The behavioural effects of an N-methylaspartate receptor antagonist following application to the iumbar spinal cord of conscious rats. Neuropharmacology 23: 719–724PubMedCrossRefGoogle Scholar
  31. Campbeli JN, Raja SN, Melyer RA, Mackinnon SE (1988) Myelinated afferents signal the hyperalgesia associated with nerve injury. Pain 32: 89–94CrossRefGoogle Scholar
  32. Cheng MK, Robertson C, Grossman RG, Foltz Williams V (1984) Neurological outcome correlated with spinal evoked potentials in a spinal cord ischemia model. J Neurosurg 60: 786–795PubMedCrossRefGoogle Scholar
  33. Chizhmakov IV, Kiskin NI, Krishtai OA, Tsyndrenko AY (1989) Glycine action on N-melhy-D-aspartate receptors in rat hippocampal neurons. Neurosci Lett 99: 331–136CrossRefGoogle Scholar
  34. Chrislensen H, Fykse EM, Fonnum F (1990) Uptake of glycine into synaptic vesicles isolated from rat spinal cord. J Neuroehem 54: 1142–1147CrossRefGoogle Scholar
  35. Cohen SA, Bidlingrneyer BA, Tarvin TL (1986) PITC derivatives in amino acid analysis. Nature 320: 769–770PubMedCrossRefGoogle Scholar
  36. Curtis DR, Hosli L, Johnston GAR (1968) A pharmacological study of depression of spinal neurones by glycine and related amino acids. Exp Brain Res 6: 1–18PubMedCrossRefGoogle Scholar
  37. Curtis DR, Duggan AW, Johnston GAR (1971) The specificity of strychnine as a glycine antagonist in the mammalian spinal cord. Exp Brain Res 12: 547–565PubMedCrossRefGoogle Scholar
  38. D’Amour F, Smith D (1941) A method for determing loss of pain sensation. J Pharmacol Exp Therap 72: 74–79Google Scholar
  39. Daiy EC, Aprison MH (1983) Glycine. In: Lajtha A (ed) Handbook of Neurochemistry. Plenum Press, New York, pp 467–499Google Scholar
  40. Davar G. Hama A, Dcykin A, Vos B, Maciewicz R (1991) MK-801 blocks the development of thermal hyperalgesia in a rat model of experimental painful neuropathy. Brain Res 553: 327–330PubMedCrossRefGoogle Scholar
  41. Davidoff RA, Graham LT, Shank RP, Werman R, Aprison MH (1967) Changes in amino acid concentrations associated with loss of spinal interneurons. J Neurochem 14: 1025–1031PubMedCrossRefGoogle Scholar
  42. Davidoff RA (1989) Mode of action of antispasticity drugs. In: Park TS, Phillips LH, Peakock WJ (eds) Management of Spasticily in Cerebral Palsy and Spinal Cord Injury. Neurosurgery: State of the art review. Hanley & Belfus, Philadelphia, pp 315–324Google Scholar
  43. Delwaide PJ (1985) Electrophysiological analysis of the mode of aciton of muscle relaxants in spasticity. Ann Neurol 17: 90–95PubMedCrossRefGoogle Scholar
  44. Dickenson AH. Sullivan AF(1990) Differential effects of excitatory amino acid antagonists on dorsal horn nociceptive neurones in the rat. Brain Res 506: 31–39PubMedCrossRefGoogle Scholar
  45. Dimitrijevic MM, Dimitrijevic MR, Sherwood AM, Vanderlinden C (1989) Clinical europhysiological techniques in the assessment of spasticity. In: Park TS, Phillips LH, Peakock WJ (eds) Physical Medicine and Rehabilitation: State of the Art Reviews.Hanley & Belfus, Philadelphia, pp 64–83Google Scholar
  46. Erdo SL (1990) Strycnine protection against excitotoxic cell death in primary cultures of rat cerebral cortex. Neurosci Lett 115: 341–344PubMedCrossRefGoogle Scholar
  47. Faganel J, Dimitrijevic MR (1982) Study of Propriospinal interneuron system in man. J Neurol Sci 56: 155–172PubMedCrossRefGoogle Scholar
  48. Fagg GE, Jordan CC, Webster RA (1978) Descending fibre-mediated release of endogenous glutamate and glycine from the perfused cat spinal cord in vivo. Brain Res 158: 159–PubMedCrossRefGoogle Scholar
  49. Fagg GE. Foster AC (1983) Amino acid neu retransmitters and their pathways in the mammalian central nervous system. Neurosciencc 9: 701–719CrossRefGoogle Scholar
  50. Farrant M, Webster RA (1989) Boulton A, Baker GB, Juorio AV (eds) Drugs as Tools in Neurotransmitter Research. Humana Press, Clifton, pp 161–219CrossRefGoogle Scholar
  51. Farrant M, Gibbs TT, Farb DH (1990) Molecular and cellular mechanisms of GABA/ Benzodiazepine-receptor regulation: Electrophysiological and biochemical studies. Neurochem Res 15: 175–191PubMedCrossRefGoogle Scholar
  52. Fasano VA, Barolat-Romana G, Zeme S, Sguazzi L (1979) Electrophysiological assessment of spinal circuits in spasticity by direct dorsal root stimulation. Neurosurgery 4: 146–151PubMedCrossRefGoogle Scholar
  53. Ganes T (1982) Synaptic and non-synaptic components of the human cervical evoked response. J Neurol Sci 4: 313–326CrossRefGoogle Scholar
  54. Gelfan S, Tarlov IM (1955) Differential vulnerability of spinal cord structures to anoxia. J Neurophysiol 18: 170–188PubMedGoogle Scholar
  55. Gerber G, Cerne R, Randic M (1991) Participation of excitatory amino acid receptors in the slow excitatory synapfic transmission in rat spinal dorsal horn. Brain Res 561: 236–251PubMedCrossRefGoogle Scholar
  56. Graham LT, Shank RP, Werman R. Aprison MH (1967) Distribution of some synaptic transmitter suspects in cat spinal cord: glutamic acid, aspartic acid, γ-aminobutyric acid, glycine, and glutamine. J Neurochem 14: 465–472PubMedCrossRefGoogle Scholar
  57. Grossi EA, Laschinger JC, Krieger KH, Nathan IM, Colvin SB, Weiss MR, Baumann FG (1988) Epidural-evoked potentials: A more specific indicator of spinal cord ischemia. J Surg Res 44: 224–228PubMedCrossRefGoogle Scholar
  58. Hall PV, Smith JE, Lane J, Mote T, Campbell R (1979) Glycine and experimental spinal spasticity. Neurology 1979; 29: 262–267PubMedCrossRefGoogle Scholar
  59. Hammerstad JP, Murray JE, Cutler RWP (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: 357–367PubMedCrossRefGoogle Scholar
  60. Hao JX, Xu XJ, Aldskogius H, Seiger A, Hallin ZW (1991) The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spina cod ischemia in the rat. Exp Neurol 113: 182–191PubMedCrossRefGoogle Scholar
  61. Hargreaves K, Dubner R, Brown F, Flores C, Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32: 77–88PubMedCrossRefGoogle Scholar
  62. Harrison PJ, Jankowska E (1985) Organization of input to the interneurons mediating group I non-reciprocal inhibition of motoneurons in the cat. Part 1. J Physiol (Lond) 361: 379–401Google Scholar
  63. Harrison PJ, Jankowska E (1985) Sources of input to interneurons mediating group 1 non-reciprocal inhibition of motorneurons in the cat. Part 2. J Physiol (Lond) 361: 403–418Google Scholar
  64. Heller AH, Hallett M (1982) Electrophysioioigcal studies with the spastic mutant mouse. Brain Res 234: 299–308PubMedCrossRefGoogle Scholar
  65. Henneman E, Mendell LM (1981) Functional organization of motorneuron pool and its inputs. In: Brookhart JM, Mountcastle VB (eds) The Nervous System, Handbook of Physiology, American Physiological Society, Bethesda, pp 423–507Google Scholar
  66. Herz DA, Looman JE, Tiberio A, Ketterling K, Kreitsch RK, Colwill HC, Grin OD (1990) The management of paralytic spasticity. Neurosurgery 26: 300–306PubMedCrossRefGoogle Scholar
  67. Hopkin J, Neal MJ (1971) Effect of electrical stimulation and high potassium concentrations on the efflux of [14C] glycine from slices of spinal cord. Br J Pharmacol 42: 215–233PubMedCrossRefGoogle Scholar
  68. Howell DA, Lees AJ, Toghill PJ (1979) Spinal internuncial neurones in progressive encephalomyelitis with rigidity. J Neurol Neurosurg Psychiatry 42: 773–785PubMedCrossRefGoogle Scholar
  69. Hunt SP (1983) Cytochemistry of the spinal cord. Tn: Emson PC (ed) Chemical Neuro-hemistry. Raven Press, New York, pp 53–84Google Scholar
  70. Juhasz G, Ernri Z, Kekesi K, Pungor K (1989) Local perfusion of the thalamus with GABA increses sleep and induces long-lasting inhibition of somatosensory event-related potentials in cats. Neurosci Lett 103: 229–23PubMedCrossRefGoogle Scholar
  71. Kajander KC, Wakisaka S, Bennett GJ (1992) Spontaneous disharge originates in the dorsal root ganglion at the onset of a painful peripheral neuropathy in the rat. Neurosci Lett 138: 225–228PubMedCrossRefGoogle Scholar
  72. Kanek M, Fukamachi A, Sasaki H, Miyazawa N, Yagishita, Nukui H (I988) Intraoperative moinitoring of the motor function: Experimental and clinical study. Acta Neurochir Scand [Suppl] 42: 18–21CrossRefGoogle Scholar
  73. Kish PE, Fischer-Bovenkerk C, Ueda T (1989) Active transport of g-aminobuiyric acid and glycine into synaptic vesicles. Proc Natl Acad Sci 86: 3877–3881PubMedCrossRefGoogle Scholar
  74. Kitagawa H, Itoh T, Takano H, Takakuwa K, Yamamoto N, Yamada H, Tsuji H (1989) Motor evoked potential monitoring during upper cervical spine surgery. Spine 14: 1078–1083PubMedCrossRefGoogle Scholar
  75. Kuypers HGJM (1973) In: Desmedt JE (ed) New Developments in Electromyography and Clinical Neurophysiology. Karger, Basel, pp 38–68Google Scholar
  76. Kuypers HGJM (1981) Anatomy of the descending pathways. In: Brookhart JM, Mountcastle VB (eds) Handbook of Physiology: The Nervous System. The American Physiological Society, Bethesda, pp 597–666Google Scholar
  77. Laird JMA, Bennett GJ (1992) Dorsal root potentials and afferent input to the spinal cord in rats with an experimental peripheral neruopathy. Brain Res 584: 181–190PubMedCrossRefGoogle Scholar
  78. Larson AA (1989) Intrathecal GABA, glycine, taurine or beta-alanine elicits dyskinetic movements in mice. Pharmaco3 Biochem Behav 32: 505–509CrossRefGoogle Scholar
  79. Lester RAJ, Tong G, Jahr CE (1993) Interactions between the glycine and glutamate binding sites of the NMDA receptor. J Neurosci 13: 1088–1096.PubMedGoogle Scholar
  80. Levy WJ, York DH, McCaffrey M, Tanzer F (1984) Motor evoked potentials from transcranial stimulation of the motor cortex in humans. Neurosurgery 15: 287–302PubMedCrossRefGoogle Scholar
  81. Lindsley DB, Schreiner LH, Magoun HW (1949) An electromyographic study of spasticity. J Neurophysiol 12: 197–205PubMedGoogle Scholar
  82. Ljungdahl A, Hokfelt T(1973) Accumulation of 3H-glycine in interneurons of the cat spinal cord. Histochemie 33: 277–280PubMedGoogle Scholar
  83. Lloyd DPC (1953) Influence of asphyxia upon the responses of spinal motorneurons. J Gen Physiol 32: 409–443CrossRefGoogle Scholar
  84. Lundberg A, Norrsell U, Voorhoeve P (1962) Pyramidal effects on lumbosacral interneur-ones activated by somatic afferents. Acta Physiol Scand 56: 220–229PubMedCrossRefGoogle Scholar
  85. Lynch DR, Anegawa NJ, Verdoorn T, Pritchett DB (1993) N-methyl-D-aspartate receptors: different subunit requirements for binding of glutamate antagonists, glycine antagonists, and channel-blocking agents. Molec Pharmacol 45: 540–545Google Scholar
  86. Magoun HW, Rhines R (1946) An inhibitory mechanism in the bulbar reticular formation. J Neurophysiol 9: 165–17PubMedGoogle Scholar
  87. Mailis A, Ashby P (1990) Alterations in group la projections to motoneurons following spinal lesions in humans. J Neurophysiol 64: 637–647PubMedGoogle Scholar
  88. Makitie J, Teravainen H (1977) Spinal cord dorsum potentials recorded in vivo after cold injury to the sural nerve in the rabbit. Cryobiology 14: 190–196PubMedCrossRefGoogle Scholar
  89. Mao J, Price DD, Mayer DJ, Lu J, Hayes RL (1992) Intrathecal MK-801 and local nerve anesthesia synergisticallyl reduce nociceplive behaviors in rats with experimental peripheral mononeuropathy. Brain Res 576: 254–262PubMedCrossRefGoogle Scholar
  90. Mao J, Price DD, Hayes RL, Lu j, Mayer DJ (1992) Differential roles of NMDA and non-NMDA receptor activation in induction and maintenance of thermal hyperalgesia in rats with painful peripheral mononeuropathy. Pain 49: 271–278Google Scholar
  91. Mao J, Price DD, Mayer DJ (1994) Thermal hyperalgesia in association with the development of morphine tolerance in rats: roles of excitatory amino acid receptors and protein kinase. C J Neurosci 14: 2301–2312Google Scholar
  92. Martiniak J. Chavko M, Danielisova V, Marsala J (1989) Regional concentrations of transmitter amino acids after spinal cord ischaemia in the rabbit. Physiol Bohemoslov 38: 275–281PubMedGoogle Scholar
  93. Masland R (1985) Preface, In: Eccles J, Dimitrijevic MR (eds) Recent Achievements in Restorative Neurology. Upper Motor Neuron Functions and Dysfunctions. Karger, Basel, xv–xviGoogle Scholar
  94. Mathias CJ, Luckitt J, Desai P, Baker H, Masri WE, Frankel HL (1989) Pharmacodynamics and pharmacokinetics of the oral antispatic agent tizanidine in patients with spinal cord injury. J Rehab Res Devel 26: 9–16Google Scholar
  95. McNamara D, Dingledine R (1990) Dual effect of glycine on NMDA-induced neuroloxicity in rat cortical cultures. I Neurosci 10: 3970–3976Google Scholar
  96. Meinck MM (1976) Occurrence of the H reflex and the F wave in the rat. Electroencephalogr Clin Neurophysiol 41:530–533PubMedCrossRefGoogle Scholar
  97. Melzack R, Wall PD (1965) Pain mechanisms: A new theory. Science 150: 971–979PubMedCrossRefGoogle Scholar
  98. Meyerson BA, Linderoth B. Karlsson H, Ungerstedi U (1990) Microdialysis in the human brain: extracellular measurements in the thalamus of parkinsonian patients. Life Sci 46: 301–308PubMedCrossRefGoogle Scholar
  99. Mitchell K, Spike RC, Todd AJ (1993) An immunocytochemical study of glycine receptor and GABA in lamine 1-III of rat spinal dorsal horn. J Neurosci 13: 2371–2381PubMedGoogle Scholar
  100. Mitchell SW, Morehouse GR, Keen WW (1864) Gunshot wounds and injuries of nerves. Lippincott, PhiladelphiaGoogle Scholar
  101. Nathan PW, Smith MC (1959) Fasciculi proprii of the spinal cord in man. Review of present knowledge. Brain 82: 610–668Google Scholar
  102. Neilson PD (1972) Interaction between voluntary contraction and tonic stretch reflex transmission in normal and spastic patients. J Neurol Neurosurg Psychiatry 35: 853–860PubMedCrossRefGoogle Scholar
  103. Nicola MA, Becker CM, Triller A (1992) Development of glycine receptor alpha subunit in cultivated rat spinal neurons: an immunocyochemical study. Neurosci Lett 138: 173–178PubMedCrossRefGoogle Scholar
  104. Nogaoka NH, Sadurada S, Sadurad T, Takeda S, Nakagawa Y, Kisara K, Arai Y (3993) Theophylline-induced nociceptive behavioral responses in mice: possible indirect interaction with spinal N-methyl-D-aspartate receptors. Neurochem Int 22: 69–74CrossRefGoogle Scholar
  105. North RB, Ewend MG, Lawton MT, Kidd DH, Piantadosi S (1991) Failed back surgery syndrome: 5-year follow-up after spinal cord stimulator implantation, Neurosurgery 28: 692–699PubMedCrossRefGoogle Scholar
  106. Panter SS, Yum SW, Faden AI (1990) Alteration in extracellular amino acids after traumatic spinal cord injury. Ann Neuroi 27: 96–99CrossRefGoogle Scholar
  107. Patel J, Zinkland WC, Thompson C, Keith R, Salama A (1990) Role of glycine in the N-methyl-D-aspartate-mediated neuronal cytotoxicity. J Neurochem 54: 849–854PubMedCrossRefGoogle Scholar
  108. Quan N, Blatteis CM (1989) Microdialysis: A system for localized drug delivery into the brain. Brain Res Bull 22: 621–625PubMedCrossRefGoogle Scholar
  109. Randall LO, Selitto JJ (1957) A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn 311: 409–419Google Scholar
  110. Rao TS, Cler JA, Emmett MR, Mick SJ, Iyengar S, Wood PL (1990) Glycine, glycinamide and D-serine act as positive modulators of signal transduction at the N-methyl-D-aspartate (NMDA) receptor in vivo: differential effects on mouse cerebellar gyclic guanosine monophosphate levels. Neuropharamacology 29: 1075–1080CrossRefGoogle Scholar
  111. Ren K, Hylden LK, Williams GM, Ruda MA, Dubner R (1992) The effects of a non-competative NMDA receptor antagonist, MK-801, on behavior hyperalgesia and dorsal horn neuronal activity in rats with unilateral inflammation. Pain 50: 331–344PubMedCrossRefGoogle Scholar
  112. Rizzoli AA (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: 11–18PubMedCrossRefGoogle Scholar
  113. Roberts P.J, Mitchell JF (1972) The release of amino acids from the hemisected spinal cord during stimulation. j Neurochem 19: 2473—2481Google Scholar
  114. Rudick RA, Breton D, Krall RL (1987) The Gaba-agonist progabide for spasticity in multiple sclerosis. Arch Neurol 44: 1033–1036PubMedCrossRefGoogle Scholar
  115. Rudomin P, Solodkin M, Jimenz I (1986) PAD and PAH response patterns of group la and Ib fibers to cutaneous and descending inputs to the cat spinal cord. J Neurophysiol 56: 987–1006PubMedGoogle Scholar
  116. Rudomin P, Solodkin M, Jimenz I (1987) Synaptic potentials of primary efferent fibers and motorneurons evoked by single intermediate nucleus interneurons in the cat spinal cord. j Neurophysiol 57: 1288–1313PubMedGoogle Scholar
  117. Rudomin P, Jimenez I, Quevedo J, Solodkin M (1990) Pharmacologic analysis of inhibition produced by last-order intermediate neucleus interneurons mediating nonreciprocal inhibition of motoneurons in cat spinal cord-j Neurophysiol 63: 147–160Google Scholar
  118. Rymer WZ, Powers RK (1989) Pathophysiology of muscular hypertonia in spasticity. Management of spasticity in cerebral palsly and spinal cord injury In: Park TS, Phillips LH, Peakock WJ (eds) Physical Medicine and Rehabilitation: State of the art reviews. Hanley & Belfus, Philadelphia, pp 291–301Google Scholar
  119. Scheardown MJ, Drejer J, Jensen LH, Stidsen CE. Honore T (1989) A potent antagonist of the strychnine inbsensitive glycine receptor has anticonvulsant properties. Europ J Pharmacol 174: 197–204CrossRefGoogle Scholar
  120. Schreiner LH, Lindsley D, Magoun HW (1949) Role of brain stem facilitatory systems in maintenance of spasticity. J Neurophysiol 12: 207–216PubMedGoogle Scholar
  121. Schwartzman RJ (1992) Reflex symmpathetic dystrophy and causalgia. The neurology of trauma. Neurologic Clin 10: 953–973Google Scholar
  122. Semba J, Patsalos PN (1993) Milacemide effects on the temporal inter-relationship of amino acids and monoamine metabolites in rat cerebrospinal fluid. Europ J Pharmacol 230: 321–326CrossRefGoogle Scholar
  123. Shank RP, Aprison MH (1970) The metabolism in vivo of glycine and serine in eight areas of the rat central nervous system. J Neurochem 17: 1461–3475PubMedCrossRefGoogle Scholar
  124. Shapovalov Al (1975) Neuronal organization and synaptic mechanisms of supraspinal motor control in vertebrates. Rev Physiol Biochem Pharmacol 72: 1–54PubMedCrossRefGoogle Scholar
  125. Sheen K, Chung JM (1993) Signs of neuropathic pain depend on signals from injured nerve fibers in a rat model. Brain Res 610: 62–68PubMedCrossRefGoogle Scholar
  126. Sher GD, Mitchell D (1990) N-methyl-D-aspartate receptors mediate responses of rat dorsal homneurones to hindlimb ischemia. Brain Res 522: 55–62PubMedCrossRefGoogle Scholar
  127. Sherrington CS, Sowion SCM (1915) Observations on reflex responses to single break shocks. J Physiol (Lond) 49: 331–348Google Scholar
  128. Shimoji K, Shimizu H, Maruyama Y (1978) Origin of somatosensory evoked responses recorded from; the cervical skin surface. J Neurosurg 48: 980–984PubMedCrossRefGoogle Scholar
  129. Shuaib A, Xu K, Grain B, Siren AL, Feuerstein G, Hallenbeck j, Davis JN (1990) Assessment of damage from implantation of microdialysis probes in the rat hippocampus with silver degeneration staining. Neurosci Lett 1 12:149–154CrossRefGoogle Scholar
  130. Simpson RK Jr. Robertson CS, Goodman JC (1989) Alterations in the corticomotor evoked potential following spinal cord ischemia. J Neurosci Meth 28: 171–178CrossRefGoogle Scholar
  131. Simpson RK Jr, Robertson CS, Goodman JC (1990) Spinal cord ischemia-induced elevation of amino acids: extracellular measurement with microdialysis. Neurochem Res 15: 635–639PubMedCrossRefGoogle Scholar
  132. Simpson RK Jr, Robertson CS, Goodman JC (1991) Segmentai release of amino acid neurotransmitters from transcranial stimulation. Neurochem Res 16: 89–94PubMedCrossRefGoogle Scholar
  133. Simpson RK Jr, Robertson CS, Goodman JC (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: 113–118Google Scholar
  134. Simpson RK Jr, Robertson CS, Goodman JC, Halter JA (1991) Recovery of amino acid neurotransmitters from the spinal cord during posterior epidural stimulation: A preliminary report. J Am Paraplegia Soc 14: 4–9Google Scholar
  135. Simpson RK Jr, Robertson CS. Goodman JC (1992) Segmental amino acid neurotransmitter recovery during posterior epidural stimulation after spinal cord injury. J Am Paraplegia Soc 16: 34–41Google Scholar
  136. Simpson RK Jr, Robertson CS. Goodman JC (3993) Glycine: An important potential component of spinal shock. Neurochem Res 18: 887–892CrossRefGoogle Scholar
  137. Simpson RK Jr, Robertson CS, Goodman JC (1993) Glycine: A potential mediator of electrically induced pain modification. Biomed Lett 48: 393–207Google Scholar
  138. Simpson RK Jr, Robertson CS, Goodman JC (1993) Spinal epidural corticomotor evoked potentials as a predictor of outcome from ischemic myelopathy. Neurol Res 15: 104–108PubMedGoogle Scholar
  139. Simpson RK Jr, Gondo MM, Robertson CS, Goodman JC (1995) The influence of glycine and related compounds on spinal cord injury induced spasticity. Neurochem Res 20: 1203–1230PubMedCrossRefGoogle Scholar
  140. Simpson RK Jr, Robertson CS, Goodman JC (1995) Reduction of mechanonociceptive and thermonociceptive responses by intrathecal administration of glycine and related compounds. Surgical Forum 46: 583–583Google Scholar
  141. Simpson RK Jr, Gondo MM, Robertson CS, Goodman JC (3 996) Reduction in the mechanonociceptive response by intrathecal administration of glycine and related compounds. Neurochem Res 21:1221–1226CrossRefGoogle Scholar
  142. Simpson RK Jr, Gondo MM, Robertson CS, Goodman JC (1996) Reduction in thermal hyperalgesia by intrathecal administration of glycine and related compounds. Neurochem Res 22: 75–79CrossRefGoogle Scholar
  143. Simpson RK Jr, Robertson CS, Goodman JC (1996) The role of glycine in spinal shock. J Spinal Cord Med 19: 215–224PubMedGoogle Scholar
  144. Smith JE, Hall PV, Galvin MR, Jones AR, Campbell RL (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: 152–356Google Scholar
  145. Song XJ, Zhao ZQ (1993) Differential effects of NMDA and non-NMDA receptor antagonists on spinal cutaneous vs muscular nociception in the cat. Neuroreport 4: 17–20PubMedCrossRefGoogle Scholar
  146. Sotgui ML (1993) Descending influence on dorsal horn neuronal hyperactivity in a rat model of neuropathic pain. Neuroreport 4: 21—24Google Scholar
  147. Sugimoto T, Bennett GJ, Kajander (1989) Strychnine-enhanced transsynaptic degeneration of dorsal horn neurons in rats with an experimental painful peripheral neuropathy. Neurosci Lett 98: 139–143PubMedCrossRefGoogle Scholar
  148. Thompson PD, Dick JPR, Asseiman R Griffin GB, Day BL, Rothwell JC, Sheehy MP, Marsden CD (1987) Examination of motor function in lesions of the spinal cord by stimulation of the motor cortex. Ann Neurol 21: 389–396PubMedCrossRefGoogle Scholar
  149. Thomson AM (1990) Glycine is a coagonisl at the NMDA receptor/channel complex. Prog Neurobiol 35: 53–74PubMedCrossRefGoogle Scholar
  150. Todd AJ (1989) Cells in laminae III and IV of rat spinal dorsal horn receive monosynaptic primary afferent input in lamina II. J Comp Neurol 289: 676–686PubMedCrossRefGoogle Scholar
  151. Turski L, Schwarz M, Turski WA, Klockgether T, Sontag KH, Collins JF (1985) Muscle relaxant action of excitatory amino acid antagonists. Neurosci Lett 53: 321–326PubMedCrossRefGoogle Scholar
  152. Turski L, Kiockgether T, Schwarz M, Sontag KH, Meldrum BS (1987) Neuroscience 20: 285–2PubMedCrossRefGoogle Scholar
  153. Van den Pol AN, Gores T (1988) Glycine and glycine receptor immunoreactivity in brain and spinal cord. J Neurosci 8: 472–492PubMedGoogle Scholar
  154. Waltz JM (1982) Computerized percutaneous multilevel spinal cord stimulation in motor disorders. Appl Neurophysiol 45: 73–92PubMedGoogle Scholar
  155. Weil S (1992) Reflex sympathetic dystrophy. In: Evans RW, Baskin DS, Yatsu FM (eds) Prognosis of Neurological Disorders. Oxford University Press, New York, pp 601–605Google Scholar
  156. Werman R, Davidoff RA, Aprison MH (1967) Evidence for glycine as the principal transmitter mediating postsynaptic inhibition in the spinal cord of the cat. J Gen Physiol 50: 1093–1094Google Scholar
  157. Werman R, Davidoff RA, Aprison MH (1968) Inhibitory action of glycine on spinal neurons in the cat. J Neurophysiol 31: 81–95PubMedGoogle Scholar
  158. Wood PL, Emmett MR, Rao TS, Mick S, Cler J, Lyengar S (1989) Part 1. J Neurochem 53: 979–98PubMedCrossRefGoogle Scholar
  159. Wood PL, Emmett MR, Rao TS, Mick S, Cler j, Lyengar S (1989) In vivo modulation of the N-methyl-D-asparlate receptor complex by D-serine: potentiation of ongoing neuronal activity as evidenced by increased cerebellar cyclic GMP. Part 2. J Neurochem 53: 982–991CrossRefGoogle Scholar
  160. Yaksh TL (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: 111–123PubMedCrossRefGoogle Scholar
  161. Yamamoto T. Yaksh TL (1992) Spinal pharmacology of thermal hyperesthesia induced by constriction injury of sicatic nerve. Excitaloryo amino acid antagonists. Pain 49: 121–128Google Scholar
  162. Yamamoto T, Yaksh TL (1993) Effects of intrathecal strychnine and bicuculline on nerve compression-induced thermal hyperalgesia and selective antagonism by MK-801. Pain 54: 79–84PubMedCrossRefGoogle Scholar
  163. Yates BJ, Thompson FJ, Mickle JP (1982) Origin and properties of spinal cord field potentials. Neurosurgery 11: 439–450PubMedCrossRefGoogle Scholar
  164. Yoneda Y, Ogita K, Suzuki T (1990) Interaction of strychnine-insensitive glycine binding with MK-801 binding in brain synaptic membranes. J Neurochem 55: 237–244PubMedCrossRefGoogle Scholar
  165. Young AB, Snyder SH (1973) Strychnine binding associated with glycine receptors of the central nervous system. Proc Nat Acad Sci 70: 2832–2836PubMedCrossRefGoogle Scholar
  166. Young AB, Macdonald RL (1987) Glycine as a spinal cord neurotransmitter. In: Davidoff RA (ed) Handbook of the spinal cord. Marcel Dekker, New York, pp 1–44Google Scholar
  167. Zeglgansberger W, Champagnat J (1979) Cat spinal motorneurones exhibit topographic sensitivity to glutamate and glycine. Brain Res 160: 95–104CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • R. K. SimpsonJr.
    • 1
  • C. S. Robertson
    • 1
  • J. Clay Goodman
    • 2
  1. 1.Departments of NeurosurgeryBaylor College of MedicineHoustonUSA
  2. 2.Departments of PathologyBaylor College of MedicineHoustonUSA

Personalised recommendations