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Pain and neurotransmitters

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Summary

  1. 1.

    To study physiological roles of substance P (SP),γ-aminobutyric acid (GABA), enkephalins and other endogenous substances, we developed several kinds of isolated spinal cord preparations of newborn rats.

  2. 2.

    In these preparations, various slow responses of spinal neurons evoked by stimulation of primary afferent C fibers were depressed by a tachykinin antagonist, spantide. These results together with many other lines of evidence suggest that SP and neurokinin A serve as pain transmitters in a subpopulation of primary afferent C fibers.

  3. 3.

    Some C-fiber responses in various isolated spinal cord preparations were depressed by GABA, muscimol, and opioid peptides. In contrast, bicuculline (GABA antagonist) and naloxone (opioid antagonist) potentiated the “tail pinch potential,” i.e., a nociceptive response of the ventral root evoked by pinch stimulation of the tail in isolated spinal cord-tail preparation of the newborn rat. The latter results support the hypothesis that some primary afferents activate inhibitory spinal interneurons which release GABA and enkephalins as transmitters to modulate pain inputs.

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References

  • Atweh, S. F., and Kuhar, M. J. (1977). Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla.Brain Res. 12453–67.

    Google Scholar 

  • Chang, M. M., Leeman, S. E., and Niall, H. D. (1971). Amino-acid sequence of substance P.Nature New Biol. 23286–87.

    Google Scholar 

  • Chang, R. S. L., and Lotti, V. J. (1986). Biochemical and pharmacological characterization of an extremely potent and selective nonpeptide cholecystokinin antagonist.Proc. Natl. Acad. Sci. USA 834923–4926.

    Google Scholar 

  • Chiu, A. T., Carini, D. J., Johnson, A. L., McCall, D. E., Price, W. A., Thoolen, M. J. M. C., Wong, P. C., Taber, R. I., and Timmermans, P. B. M. W. M. (1988). Non-peptide angiotensin II receptor antagonists. II. Pharmocology of S-8308.Eur. J. Pharmacol. 15713–21.

    Google Scholar 

  • Cuello, A. C., Polak, J. M., and Pearse, A. G. E. (1976). Substance P: A naturally occurring transmitter in human spinal cord.Lancet 21054–1056.

    Google Scholar 

  • De Biasi, 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 857820–7824.

    Google Scholar 

  • DiFiglia, M., Aronin, N., and Leeman, S. E. (1982). Light microscopic and ultrastructural localization of immunoreactive substance P in the dorsal horn of monkey spinal cord.Neuroscience 71127–1139.

    Google Scholar 

  • Duggan, A. W., Morton, C. R., Zhao, Z. Q., and Hendry, I. A. (1987). Noxious heating of the skin releases immunoreactive substance P in the substantia gelatinosa of the cat: A study with antibody microprobes.Brain Res. 403345–349.

    Google Scholar 

  • Dun, N. J., and Jiang, Z. G. (1982). Non-cholinergic excitatory transmission in inferior mesenteric ganglia of the guinea pig: Possible mediation by substance P.J. Physiol. 325145–159.

    Google Scholar 

  • Elliott, T. R. (1904). On the action of adrenalin.J. Physiol. 31xx-xxi.

    Google Scholar 

  • Euler, U. S. v., and Gaddum, J. H. (1931). An unidentified depressor substance in certain tissue extracts.J. Physiol. 7274–87.

    Google Scholar 

  • Helke, C. J., Charlton, C. G., and Wiley, R. G. (1986). Studies on the cellular localization of spinal cord substance P receptors.Neuroscience 19523–533.

    Google Scholar 

  • Hökfelt, T., Kellerth, J-O., Nilsson, G., and Pernow, B. (1975). Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons.Brain Res. 100235–252.

    Google Scholar 

  • Hökfelt, T., Ljungdahl, A., Terenius, L., Elde, R., and Nilsson, G. (1977). Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: Enkephalin and substance P.Proc. Natl. Acad. Sci. USA 743081–3085.

    Google Scholar 

  • Jessell, T. M., and Iversen, L. L. (1977). Opiate analgesics inhibit substance P release from rat trigeminal nucleus.Nature 268549–551.

    Google Scholar 

  • Konishi, S., and Otsuka, M. (1985). Blockade of slow excitatory post-synaptic potential by substance P antagonists in guinea pig sympathetic ganglia.J. Physiol. 361115–130.

    Google Scholar 

  • Konishi, S., Tsunoo, A., and Otsuka, M. (1979). Substance P and noncholinergic excitatory synaptic transmission in guinea pig sympathetic ganglia.Proc. Jap. Acad. 55B525–530.

    Google Scholar 

  • Konishi, S., Tsunoo, A., and Otsuka, M. (1981). Enkephalin as a transmitter for presynaptic inhibition in sympathetic ganglia.Nature 29480–82.

    Google Scholar 

  • Kuraishi, Y., Hirota, N., Sato, Y., Hanashima, N., Takagi, H., and Satoh, M. (1989). Stimulus specificity of peripherally evoked substance P release from the rabbit dorsal horn in situ.Neuroscience 30241–250.

    Google Scholar 

  • LaMotte, C. C., and de Lanerolle, N. C. (1983). Ultrastructure of chemically defined neuron systems in the dorsal horn of the monkey. II. Methionine-enkephalin immunoreactivity.Brain Res. 27451–63.

    Google Scholar 

  • Lembeck, F. (1953). Zur Frage der zentralen Übertragung afferenter Impulse. III. Mitteilung. Das Vorkommen und die Bedeutung der Substanz P in den dorsalen Wurzeln des Rückenmarks.Arch. exp. Path. Pharmakol. 219197–213.

    Google Scholar 

  • Lynn, B., and Hunt, S. P. (1984). Afferent C-fibres: Physiological and biochemical correlations.Trends NeuroSci. 7186–188.

    Google Scholar 

  • Matsuto, T., Yanagisawa, M., Otsuka, M., Kanazawa, I., and Munekata, E. (1984). The excitatory action of the newly-discovered mammalian tachykinins, neurokininα and neurokininβ, on neurons of the isolated spinal cord of the newborn rat.Neurosci. Res. 2105–110.

    Google Scholar 

  • Melzack, R., and Wall, P. D. (1965). Pain mechanisms: A new theory. A gate control system modulates sensory input from the skin before it evokes pain perception and response.Science 150971–979.

    Google Scholar 

  • Miyata, Y., and Otsuka, M. (1975). Quantitative histochemistry ofγ-aminobutyric acid in cat spinal cord with special reference to presynaptic inhibition.J. Neurochem. 25239–244.

    Google Scholar 

  • Morris, R. (1985). Evidence for the possible involvement ofγ-aminobutyric acid (GABA) in cutaneous and muscle-nerve-evoked inhibitions of responses of cat spinal neurones to noxious thermal stimulation.J. Physiol. 364:42P.

    Google Scholar 

  • Nagy, J. I., Hunt, S. P., Iversen, L. L., and Emson, P. C. (1981). Biochemical and anatomical observations on the degeneration of peptide-containing primary afferent neurons after neonatal capsaicin.Neuroscience 61923–1934.

    Google Scholar 

  • Nowak, L. M., and Macdonald, R. L. (1982). Substance P: Ionic basis for depolarizing responses of mouse spinal cord neurons in cell culture.J. Neurosci. 21119–1128.

    Google Scholar 

  • Nussbaumer, J.-C., Yanagisawa, M., and Otsuka, M. (1989). Pharmacological properties of a C-fibre response evoked by saphenous nerve stimulation in an isolated spinal cord-nerve preparation of the newborn rat.Br. J. Pharmacol. 98373–382.

    Google Scholar 

  • Nyberg, F., Vaeröy, H., and Terenius, L. (1988). Opioid peptides and substance P in the cerebrospinal fluid regulation and significance to pain. InBasic Mechanisms of Headache (J. Olesen and L. Edvinsson, Eds.), Elsevier, Amsterdam, pp. 241–258.

    Google Scholar 

  • Otsuka, M., and Konishi, S. (1976a). Release of substance P-like immunoreactivity from isolated spinal cord of newborn rat.Nature 26483–84.

    Google Scholar 

  • Otsuka, M., and Konishi, S. (1976b). Substance P and excitatory transmitter of primary sensory neurons.Cold Spring Harbor Symp. Quant. Biol. 40135–143.

    Google Scholar 

  • Otsuka, M., and Yanagisawa, M. (1987a). Does substance P act as a pain transmitter?Trends Pharamacol. Sci. 8506–510.

    Google Scholar 

  • Otsuka, M., and Yanagisawa, M. (1987b). Effect of a substance P antagonist on capsaicin-induced nociceptive reflex in the isolated spinal cord-tail preparation of the rat.Acta Physiol. Hung. 69363–366.

    Google Scholar 

  • Otsuka, M., and Yanagisawa, M. (1987c). The roles of neuropeptides in spinal nociceptive mechanisms: New approaches using isolated CNS preparations. InPharmacology (M. J. Rand and C. Raper, Eds.), Elsevier, Amsterdam, pp. 211–214.

    Google Scholar 

  • Otsuka, M., and Yanagisawa, M. (1988). Effect of a tachykinin antagonist on a nociceptive reflex in the isolated spinal cord-tail preparation of the newborn rat.J. Physiol. 395255–270.

    Google Scholar 

  • Pernow, B. (1953). Studies on substance P. Purification, occurrence and biological actions.Acta Physiol. Scand. 29 (Suppl. 105):1–90.

    Google Scholar 

  • Price, G. W., Wilkin, G. P., Turnbull, M. J., and Bowery, N. G. (1984). Are baclofen-sensitive GABAB receptors present on primary afferent terminals of the spinal cord?Nature 30771–74.

    Google Scholar 

  • Randić, M., Murase, K., Ryu, P. D., and Gerber, G. (1987). Slow excitatory transmission in the rat spinal dorsal horn: Possible mediation by tachykinins.Biomed. Res. 8 (Suppl.):71–82.

    Google Scholar 

  • Rosell, S., Björkroth, U., and Folkers, K. (1983). Subpopulations of substance P (SP) receptors and separate eledoisin receptors. InSubstance P—Dublin 1983 (P. Skrabanek and D. Powell, Eds.), Boole Press, Dublin, pp. 61–62.

    Google Scholar 

  • Snyder, S. H. (1980). Brain peptides as neurotransmitters.Science 209976–983.

    Google Scholar 

  • Takahashi, T., and Otsuka, M. (1975). Regional distribution of substance P in the spinal cord and nerve roots of the cat and the effect of dorsal root section.Brain Res. 871–11.

    Google Scholar 

  • Tsunoo, A., Konishi, S., and Otsuka, M. (1982). Substance P as an excitatory transmitter of primary afferent neurons in guinea pig sympathetic ganglia.Neuroscience 72025–2037.

    Google Scholar 

  • Tuchscherer, M. M., and Seybold, V. S. (1985). Immunohistochemical studies of substance P, cholecystokinin-octapeptide and somatostatin in dorsal root ganglia of the rat.Neuroscience 14593–605.

    Google Scholar 

  • Woolf, C. J., and Fitzgerald, M. (1982). Do opioid peptides mediate a presynaptic control of C-fibre transmission in the rat spinal cord?Neurosci. Lett. 2967–72.

    Google Scholar 

  • Yaksh, T. L., Jessell, T. M., Gamse, R., Mudge, A. W., and Leeman, S. E. (1980). Intrathecal morphine inhibits substance P release from mammalian spinal cord in vivo.Nature 286155–157.

    Google Scholar 

  • Yanagisawa, M., and Otsuka, M. (1984). The effect of a substance P antagonist on chemically induced nociceptive reflex in the isolated spinal cord-tail preparation of the newborn rat.Proc. Jap. Acad. 60B427–430.

    Google Scholar 

  • Yanagisawa, M., and Otsuka, M. (1988) An isolated spinal cord-saphenous nerve-skin preparation of the neonatal rat and the effects of spantide on capsaicin-induced nociceptive reflex.Neurosci. Res. Suppl. 7:S140.

    Google Scholar 

  • Yanagisawa, M., Otsuka, M., and Garcia-Arraras, J. E. (1986). Effects of GABA and GABA-related drugs on the capsaicin-induced nociceptive reflex in the isolated spinal cord-tail preparation of the newborn rat.Neurosci. Res. Suppl. 3:S127.

    Google Scholar 

  • Yanagisawa, M., Murakoshi, T., Tamai, S., and Otsuka, M. (1984). Tail-pinch method in vitro and the effects of some antinociceptive compounds.Eur. J. Pharmacol. 106231–239.

    Google Scholar 

  • Yoshioka, K., and Otsuka, M. (1989). Muscarinic presynaptic inhibition of the monosynaptic reflex is evoked by activation of tachykinin-containing primary afferents.Jpn. J. Pharmacol. 49 (Suppl.):301P.

    Google Scholar 

  • Young, W. S., III, and Kuhar, M. J. (1980). Radiohistochemical localization of benzodiazepine receptors in rat brain.J. Pharmacol. Exp. Ther. 212337–346.

    Google Scholar 

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  1. Department of Pharmacolgy, Faculty of Medicine, Tokyo Medical and Dental University, 113, Tokyo, Japan

    Masanori Otsuka & Mitsuhiko Yanagisawa

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  1. Masanori Otsuka
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  2. Mitsuhiko Yanagisawa
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Otsuka, M., Yanagisawa, M. Pain and neurotransmitters. Cell Mol Neurobiol 10, 293–302 (1990). https://doi.org/10.1007/BF00711176

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