Opioid Receptors in the Dorsal Horn of Intact and Deafferented Rats: Autoradiographic and Electrophysiological Studies

  • J. M. Besson
  • M. C. Lombard
  • J. M. Zajac
  • D. Besse
  • M. Peschanski
  • B. P. Roques


The direct depressive effect of opioids on the transmission of nociceptive processing at the spinal level is well documented (see refs in Le Bars and Besson, 1981; Duggan and North, 1984; Yaksh and Noueihed, 1985; Zieglgänsberger, 1986; Besson and Chaouch, 1987). Both pre- and postsynaptic mechanisms have been proposed as an explanation of the depressive effects of opioids on the activity of nociceptive dorsal horn neurons. Despite the lack of morphological evidence for a direct presynaptic control by enkephalinergic axo-axonic synapses, there is evidence for a presynaptic action of opioid substances (Fields et al, 1980; Jessell and Iversen, 1977; Lamotte et al, 1976; MacDonald and Nelson, 1978; Mudge et al, 1979; Sastry, 1979). In addition both electrophysiological (Barker et al, 1978; Zieglgänsberger and Tulloch, 1979; Yoshimura and North, 1983) and immunocytochemical (Aronin et al, 1981; Hunt et al, 1980; Ruda, 1982; Ruda et al, 1984) investigations support postsynaptic sites of action of opioids.


Opioid Receptor Dorsal Horn Opiate Receptor Dorsal Horn Neuron Superficial Dorsal Horn 
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. AANONSEN, L. M., WILCOX, G. L., (1987) Nociceptive action of excitatory aminoacids in the mouse: effects of spinally administered opioids, phencyclidine and sigma agonists. J.Pharmacol Exp. Ther, 2439–19.Google Scholar
  2. ARNER, S. and MEYERSON, B. A., (1988). Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain, 33, 11–23.CrossRefGoogle Scholar
  3. ARONIN, N., DIFIGLIA, M., LIOTTA, A. S., and MARTIN, J. S. (1981). Ultrastructural localization and biochemical features of immunoreactive leu-enkephalin in monkey dorsal horn. J. Neurosci. 1, 561–577.Google Scholar
  4. ATWEH, S. F. and KUHAR, M. J. (1977). Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla. Brain Res., 124, 53–67.CrossRefGoogle Scholar
  5. BARKER, J. L., GRUOL, D. L., HUANG, M., MACDONALD, J. F., and SMITH, T. G. (1980). Peptide receptor functions on cultured spinal neurons. In Neural Peptides and Neuronal Communications. E. Costa and M. Trabucchi, eds., pp. 409–423, Raven Press, New York.Google Scholar
  6. BARKER, J. L., SMITH, T. G. and NEALE, J. H. (1978). Multiple membrane actions of enkephalin revealed using cultured spinal neurons. Brain Res., 154–158.Google Scholar
  7. BESSON, J. M. and CHAOUCH, A. (1987). Peripheral and spinal mechanisms of nociception. Physiol Rev., 67, 67–185.Google Scholar
  8. CSILLIK, B. and KNYIHAR-CSILLIK, E. (1986). The Protean Gate. Akademiai Kiado, Budapest.Google Scholar
  9. CZLONKOWSKI, A., COSTA, T., PRZEWLOCKI, R., PASI, A. and HERZ, A. (1983). Opiate receptor binding sites in human spinal cord. Brain Res. 267, 392–296.CrossRefGoogle Scholar
  10. DAVAL, G., VERGE, D. and BASBAUM, A. I., BOURGOIN, S. and HAMON, M. (1987). Autoradiographic evidence of serotonin binding sites on primary afferent fibres in the dorsal horn of the rat spinal cord. Neurosci. Lett., 83, 71–76.Google Scholar
  11. DELAY-GO YET, P., ROQUES, B. P. and ZAJAC, J. M. (1987). Differences of binding characteristics of non-selective opiates towards µand δreceptors types. Life Sci., 441, 723–731.CrossRefGoogle Scholar
  12. DUGGAN, A. W., HALL, J. W. and HEADLEY, P. M. (1977). Suppression of transmission of nociceptive impulses by morphine: selective effects of morphine administered in the region of the substantia gelatinosa. Brit. J. Pharmacol., 61, 65–76Google Scholar
  13. DUGGAN, A. W. and NORTH, R. A. (1984). Electrophysiology of opioids, Pharmacol Rev., 35, 219–281.Google Scholar
  14. FEILDS, H. L., EMSON, P. C., LEIGH, B. K., GILBERT, R.F.T. and IVERSEN, L. L. (1980). Multiple opiate receptor sites on primary afferent fibres. Nature, 284, 351–353.CrossRefGoogle Scholar
  15. FITZGERALD, M. (1984). The course and termination of primary afferent fibers. In Textbook of Pain. Edited by P. D. Wall and R. Melzack, Churchill Linvingstone, pp. 34–48.Google Scholar
  16. GAMSE, R., HOLZER, P. and LEMBECK, F. (1979). Indirect evidence for presynaptic location of opiate receptors on chemosensitive primary sensory neurones. Naunyn-Schmiedeberg’s Arch. Pharmacol., 308, 281–285.CrossRefGoogle Scholar
  17. GOODMAN, R. R., SNYDER, S. H., KUHAR, S. H. and YOUNG, W. S. III (1980). Differentiation of d and µopiate receptor localization by light microscopic autoradiography, Proc. Natl. Acad. Sci. U.S.A., 77, 6239–6243.CrossRefGoogle Scholar
  18. GOUARDERES, C, CROS, J. and QUIRION, R. (1985). Autoradiographic localization of µ, δand κ opioid receptor binding sites in rat and guinea pig spinal cord. Neuropeptides, 6, 331–342.CrossRefGoogle Scholar
  19. GUILBAUD, G., IGGO, A. and TEGNER, R. (1985). Sensory receptors in ankle joint capsules of normal and arthritic rats. Exp. Brain Res., 58, 29–40.CrossRefGoogle Scholar
  20. HILLER, J. M., SIMON, E. J., CRAIN, S. M. and PETERSEN, E. R. (1978). Opiate receptors in cultures of fetal mouse dorsal root ganglia (DRG) and spinal cord: DRG neurites. Brain Res., 145, 396–400.CrossRefGoogle Scholar
  21. 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. Nat. Acad. Sci. U. S.A., 74, 3081–3085.CrossRefGoogle Scholar
  22. HUNT, S. P., KELLY, J. S. and EMSON, P. C. (1980). The electron microscopic localization of methionine enkephalin within the superficial layers (I and II) of the spinal cord. Neuroscience 5, 1871–1890.CrossRefGoogle Scholar
  23. HYLDEN, J. L. K. and WILCOX, G. L. (1983). Pharmacological characterization of substance P-induced nociception in mice: modulation by opioid and noradrenergic agonists at the spinal level. J. Pharmacol. Exp. Ther., 226, 398–404.Google Scholar
  24. JESSELL, T. M. and IVERSEN, L. L. (1977). Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature, 268, 549–551.CrossRefGoogle Scholar
  25. JESSELL, T., TSUNOO, A., KANAZAWA, I. and OTSUKA, K. (1979). Substance P: Depletion in the dorsal horn of rat spinal cord after section of the peripheral processes of primary sensory neurons. Brain Res., 168, 247–259.CrossRefGoogle Scholar
  26. LAMOTTE, C., PERT, C. B. and SNYDER, S. H. (1976). Opiate receptor binding in primate spinal cord; Distribution and changes after dorsal root section. Brain Res., 112, 407–412.CrossRefGoogle Scholar
  27. LE BARS, D. and BESSON, J. M. (1981). The spinal site of action of morphine in pain relief: from basic research to clinical applications. Trends in Pharmacol. Sciences2, 323–325.CrossRefGoogle Scholar
  28. LOMBARD, M. C. and LARABI, Y. (1983). Electrophysiological study of cervical dorsal horn cells in partially deafferented rat. In Advances in pain Research and therapy, vol.5, edited by J. J. Bonica et al, Raven Press, New York, pp. 147–153.Google Scholar
  29. MACDONALD, R. L. and NELSON, P. G. (1978). Specific opiate-induced depression of transmitter release from dorsal root ganglion cells in culture. Science, 199, 1449–11451.CrossRefGoogle Scholar
  30. MACK, K. J. KILLIAN, A. and NEYHENMEYER, J. A. (1984). Comparison of µ, δ and κ opiate binding sited in rat brain and spinal cord. Life Sci., 34, 281–285.CrossRefGoogle Scholar
  31. MENÉTREY, D. and BESSON, J. M. (1982). Electrophysiological characteristics of dorsal horn cells in rats with cutaneous inflammation resulting from chronic arthritis. Pain, 13, 343–364.CrossRefGoogle Scholar
  32. MORRIS, B. J. and HERZ, A. (1987). Distinct distribution of opioid receptor types in rat lumbar spinal cord. Naumyn-Schmiedeberg’s Arch. Pharmacol, 336, 240–243.CrossRefGoogle Scholar
  33. MORTON, C. R., ZHAO, Z.Q. and DUGGAN, A. (1987). Kelatorphan potentiates the effect of (Met) enkephalin in the substantia gelatinosa of the cat spinal cord. Eur. J. Pharmacol., 140, 195–201.CrossRefGoogle Scholar
  34. MUDGE, A. W., LEEMAN, S. E. and FISCHBACH, G. D. (1979). Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration. Proc. Natl. Acad. Sci. U.S.A., 76, 526–530.CrossRefGoogle Scholar
  35. NAGY, J. I., Vincent, S. R., STAINES, W. M., FIBIGER, H. C, REISINE, T. D. and YAMAMURA, H. I. (1980). Neurotoxic action of capsaicin on spinal substance P neurons. Brain Res., 186, 435–444.CrossRefGoogle Scholar
  36. NINKOVIC, M., HUNT, S. P. and GLEAVE, J. R. W. (1982). Localization of opiate and histamine H1-receptors in the primate sensory ganglia and spinal cord. Brain Research, 241, 197–206.CrossRefGoogle Scholar
  37. NINKOVIC, M., HUNT, S. P. and KELLY, J. S. (1981). Effect of dorsal rhizotomy on autoradiographic distribution of opiate and neurotensin receptors and neurotensin-like immunoreactivity within the rat spinal cord. Brain Res., 230, 111–119.CrossRefGoogle Scholar
  38. PEARSON, J., BRANDEIS, L., SIMON, E. and HILLER, J. (1980). Radioautography of binding of tritiated diprenorphine to opiate receptors in the rat. Life Sciences 26, 1047–1052.CrossRefGoogle Scholar
  39. PERT, C. B., KUHAR, M. J. and SNYDER, S. H. (1975). Autoradiographic localization of the opiate receptor in rat brain. Life Sci., 16, 1849–1854.CrossRefGoogle Scholar
  40. PERT, C. B. KUHAR, M. J. and SNYDER, S. H. (1976). Opiate receptor: Autoradiographic localization in rat brain. Proc. Natl. Acad. Sci. U.S.A., 73, 3729–3733.CrossRefGoogle Scholar
  41. RUDA, M. A. (1982). Opiates and pain pathways: demonstration of enkephalin synapses on dorsal horn projection neurones, Science, 215, 1523–1525.CrossRefGoogle Scholar
  42. RUDA, M. A., COFFIELD, J. and DUBNER, R. (1984). Demonstration of postsynaptic opioid modulation of thalamic projection neurons by the combined techniques of retrograde horseradish peroxidase and enkephalin immunohistochemistry, J. Neurosci, 4, 2117–2132.Google Scholar
  43. SASTRY, B. R. (1979). Presynaptic effects of morphine and methionine-enkephalin in feline spinal cord. Neuropharmacology, 18, 367–375.CrossRefGoogle Scholar
  44. SLATER, P. and PATEL, S. (1983). Autoradiographic localization of opiate κ receptors in the rat spinal cord. Eur. J. Pharmacol, 92, 159–160.CrossRefGoogle Scholar
  45. TASKER, R. R. (1984). Deafferentation. In Textbook of Pain. Edited by P. D. Wall and R. Melzack, Churchill Linvingstone, pp. 119–132.Google Scholar
  46. TRAYNOR, J. R. and WOOD, M. S. (1987). Distribution of opioid binding sites in spinal cord. Neuropeptides, 10, 313–320.CrossRefGoogle Scholar
  47. WAKSMAN, G., HAMEL, E., DELAY-GOYET, P. and ROQUES, B.P. (1987). Neutral endopeptidase 24.11 µ and δ opioid receptors after selective brain lesions: an autoradiographic study. Brain Res., 436, 205–216. Google Scholar
  48. WAKSMAN, G., HAMEL, E., FOURNIE-ZALUSKI, M. C. and ROQUES, B. P. (1986). Autoradiographic comparison of the distribution of the neutral endopeptidase enkephalinaseand of µand δopioid receptors in rat brain. Proc. Natl Acad. Sci. (USA), 86, 1523–1527.CrossRefGoogle Scholar
  49. WAMSLEY, J. K. (1983) Opioid receptors: autoradiography. Physiol Rev. 35, 69–83Google Scholar
  50. WAMSLEY, J. K., ZARBIN, M. A., YOUNG, W. S. and MUHAR, M. J. (1982). Distribution of opiate receptors in the monkey brain: an autoradiographic study. Neurosci., 7, 595–613.CrossRefGoogle Scholar
  51. WILLCOCKSON, W. S., KIM, J., SHIN, H. K., CHUNG, J. M. and WILLIS, W. D. (1986). Actions of opioids on primate spinothalamic tract neurones. J. Neurosci., 6, 2509–2520.Google Scholar
  52. YAKSH, T. L. and NOUEIED, R. (1985). The physiology and pharmacology of spinal opiates. Ann. Rev. Pharmacol Toxicol, 25, 433–462.CrossRefGoogle Scholar
  53. YOUNG, W. S. III, WAMSLEY, J. K., ZARBIN, M. A. and KUHAR, M. J. (1980). Opioid receptors undergo axonal flow. Science, 210, 76–77.CrossRefGoogle Scholar
  54. YOSHIMURA, M. and NORTH, R. A. (1983). Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature, 305, 529–530.CrossRefGoogle Scholar
  55. ZAJAC, J. M., GACEL, J., PETIT, F., DODEY, P., ROSSIGNOL, P. and ROQUES, B. P. (1983). Deltakephalin, TYR-D-THR-GLY-PHE-LEU-THR: A new highly potent and fully specific agonist for opiate-receptors. Biochem. Biophys. Res. Comm., 11, 390–397.CrossRefGoogle Scholar
  56. ZAJAC, J. M. and ROQUES, B. P. (1989). Properties required for reversible and irreversible radiolabeled probes for selective characterization of brain receptors and peptidase by autoradiography. In Brain imaging: Techniques and Applications, Eds. Shariff, N. A. and Lewis, M. E., Ellis Horwood Ltd.Google Scholar
  57. ZIEGLGANSBERGER, W. (1986). Central control of nociception. In: Handbook of Physiology, The nervous system IV. V. B. Mountcastle, F. E. Bloom, S. R. Geiger (eds.), Williams and Wilkins, Baltimore.Google Scholar
  58. ZIEGLGANSBERGER, W. and BAYERL, H. (1976). The mechanism of inhibition of neuronal activity by opiates in the spinal cord of the cat. Brain Res., 115, 111–128.CrossRefGoogle Scholar
  59. ZIEGLGANSBERGER, W. and TULLOCH, I. F. (1979). The effects of methionine- and leucine-enkephalin on spinal neurones of the cat. Brain Res., 167, 53–64.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • J. M. Besson
    • 1
    • 2
  • M. C. Lombard
    • 1
    • 2
  • J. M. Zajac
    • 3
  • D. Besse
    • 1
    • 2
  • M. Peschanski
    • 1
  • B. P. Roques
    • 3
  1. 1.Unité de Recherche de Neurophysiologie Pharmacologique (I.N.S.E.R.M., U.161),ParisFrance
  2. 2.Laboratoire de Physiopharmacologie de la DouleurEcole Pratique des Hautes EtudesParisFrance
  3. 3.Unité de Recherche de Pharmacochimie Moléculaire (I.N.S.E.R.M., U.266 and C.N.R.S. UA 498)ParisFrance

Personalised recommendations