Abstract
Early behavioural and neurochemical studies suggested the involvement of tryptophan (TRP) in the mechanisms of analgesia. These studies were followed by an impressive number of experiments on the possible involvement of serotonin (5-HT) in this phenomenom. However the physiological role of the serotonin system(s) in pain and analgesia remained to be clarified. During the last decade the role of the excitatory amino acids in the transmisson of nociceptive messages at spinal level was clearly established. During the same period, parallel studies suggested that the second route of trytophan metabolism e.g the kynurenine pathway, is involved in the control of neuronal activity. Considered simultaneously these different studies lead to the idea that metabolites of kynurenine e.g kynurenic acid (KYN) and quinolinic acid (QUIN), endogenous ligands of excitatory amino acids receptors, might play a role in analgesia and nociception. This paper discusses some recent data related to the possible respective roles of 5-HT and kynurenine derivatives in pain mechanisms at the spinal level.
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Reference
Ault, B.A. and Hildebrand, L. M., 1993, Effects of excitatory amino acid receptor antagonists on a capsaicinevoked nociceptive reflex: a comparison with morphine, clonidine and baclofen,Pain, 52: 341.
Cesselin, F., Laporte, A.M., Miquel, M.C., Bourgoin, S., and Hamon, M., 1994, Serotonergic mechanisms of pain control,in:“Progress in Pain Research Therapy”, G.F. Gebhart, L., Hammond and T.S. Jensen, edts, IASP Press, Seattle. pp 669
Chiang, C.Y and Xiang, X.K., 1987, Does morphine enhance the release of 5-HT in the rat spinal cord? An in vivo differential pulse voltametry study,Brain Research., 411: 259.
Coderre, T.J. and Van Empel, IN The utility of excitatory amino acid (EAA) antagonists as analgesic agents. II. Assesment of the antinociceptive activity of combinations of competitive and non competitive NMDA antagonists with agents acting at allosteric-glycine and polyamine receptor sites,Pain. 1994, 59: 353
Dray, A., 1994, Chemical activation and sensitization of nociceptors, in: Peripheral neurons in nociception: physio-pharmacological aspects, J.M Besson, G. Guilbaut, H. Ollat, edts, John Libbey Eurotext, Paris. pp 49–70
Elmslie, K.S., and Yoshikami, D., 1985, Effect of kynurenate on root potentials evoked by synaptic activity and amino acids in the frog spinal cordBrain Research. 330: 265.
Gannong, A.H., LanthornT.H., and Cotman, C. W., 1983, Kynurenic acid inhibits the synaptic and amino acid-induced responses in the rat hippocampus and spinal cord,Brain Research, 273: 170.
Godefroy F., Matson W.R., Gamache P.H., and Weil-Fu azza J., 1990, Simultaneous measurements of tryptophan and its metabolites, kynurenine and serotonin, in the superficial layers of the spinal dorsal horn. A study in normal and arthritic ratsBrain Research, 526: 169.
Groppeti A., Braga P.C., Biella G.,Parenti M., Rusconi L and Mantegazza, P., 1988, Effect of aspirin on serotonin and met-enkephalin in brain: correlation with the an anyinociceptive activity of the drug,Neuropharmacology, 27: 499.
Heyes M.P. Saito, K., Crowle, J.S., Davis, L.E,. Demitrac, M.A,. Der, M., Dillin, A,. Elia, J,. Kruesi,M.J.P.,. et al., 1992, Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological diseaseBrain115:1249
Jahr, C.E. and Jessel, T.M., 1985, Synaptic transmission between dorsal root ganglion and spinal dorsal horn in cultures: antagonist of monosynaptic excitatory post synaptic potentials and glutamate excitation by kynurenateJ. Neurosci. 5: 2281.
Le Bars D . 1988, Serotonin and painin: “Neuronal serotonin”, N.N. Osborne and M. Hamon edts, John Wiley & Sons Ltd. pp: 171–119
McKormack., K.M., 1994, Non-steroidal anti-inflammatory drugs and spinal nociceptive processing.,Pain, 59: 9.
Matos, F.F., Rollema, H., Brown, J.L. and Basbaum, A.I.,1992, Do opioids evoke the release of serotonin in the spinal cord? An in vivo microdyalisis study on the regulation of the extracellular serotonin in the rat,Pain, 48: 439
Messing, R.B., Flincchbaugh, C. and Waymire. J.C. 1978, Tryptophan and 5-hydroxyindoles in different CNS regions fpllowin acute morphine,Eur. J. Pharmacol.48: 137.
Milan MT 1994, Serotonin and Pain: evidence that activation of 5-HTIA receptors does not elicit antinociception against noxious thermal mechanical and chemical stimuli in micePain 58: 45.
Moroni F . Russi P. Gallo-Mezo M.A. Moneti, G. and Pellicciari, R. 1991, Modulation of quinolinic and kynurenic acid content in the rat brain: effects of endotoxins and nicotinylalanine,J. Neurochem., 57:1630
Saito, K., Nowak, T.S. Suyama, K, Queany, B.J., Saito, M., Crowley, J.S., Markey, P.S., and M.P., Heyes., 1993, Kynurenine pathway enzymzs in brain: responses to ischemic brain injury versus systemic immune activation,Journal o Neurochemistry, 61: 2061
Samamin R . Miranda F. and Mennini T. 1972, Serotonergic mechanismsof naecotic actin in “Factors affecting the actions of narcotics”, M.L. Adler, L. Manara and R. Samamin, edts., Raven Press New York. pp. 523–539
Stone T.W. and Connick J.H. Effects of quinolinic and kynurenic acids on central neurons. 1991 in: “Kynurenine and serotonin pathways”, R. Schwartz, S.N. Youg and R. Brown, edts, Plenum Press, New York and london, pp. 329–336
Swartz, K. J., During, M.T., Freese, A, and Beal, M. F.,1990, Cerbral synthesis and release of kynurenic acid: an endogenous antagonist of excitatory amino acid receptors,J of Neuroscience, 10: 2965
Tagliamonte, A. Biggio, G., Vargiu, L. and Gessa, G.L.,1973, Increase of brain tryptophan and stimulation of serotonin synthesis by salicylate,J Neurochem., 20: 909
Tohyama M. Kitama H., Satoh K Araki T, Maeno H Oyamada H. and Kondo E. 1994, Glutamergic neurotransmission, proto-oncogenes, and pain. in: “Progress in Pain Research Therapy”, G.F. Gebhart, D.L., Hammond and T.S. Jensen, edts, IASP Press, Seattle. pp: 395–410
Weil-Fugazza, J., Godefroy, F. and Besson, J.M.,1979, Changes in brain and spinal tryptophan and 5-hydroxyindoleacetic acid levels following acute morphine administration in normal and arthritic rats,Brain Res., 175: 291
Weil-Fugazza J. Godefroy F. Coudert. D. and Besson J.M. 1981 Total and free tryptophan levels in serum following acute morphine administration in arthritic rats,Neurochem. Intern., 3: 323
Weil-Fugazza, J. and Godefroy.F., 1993, Dorsal and ventral dopaminergic innervation of the spinal cord: functional implications,Brain Res. Bull., 30: 319.
Wilcox G.L ., 1991, Excitatory neurotransmitters in pain,in“Pain research and clinical management” M.R. Bond and J.E. Charlton edts., Elsevier Amsterdam. pp. 97–117
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© 1996 Plenum Press, New York
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Weil-Fugazza, J. (1996). Endogenous Kynurenine Derivatives and Pain. In: Filippini, G.A., Costa, C.V.L., Bertazzo, A. (eds) Recent Advances in Tryptophan Research. Advances in Experimental Medicine and Biology, vol 398. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0381-7_11
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DOI: https://doi.org/10.1007/978-1-4613-0381-7_11
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