Abstract
Recent technical innovations have advanced the study of the mechanisms of pain and analgesia. These advances have resulted in an increased understanding of the anatomical organization of the dorsal horn at the medullary and spinal levels. Studies employing immunocytochemical labeling of neurotransmitters, retrograde transport of HRP, and intracellular HRP techniques have been at the forefront. The greatest strides, however, have been made when two of these approaches were combined in a single experiment to identify relationships between two labeled elements simultaneously. Many of the multiple-label experiments that were first accomplished in the dorsal horn are applicable throughout the nervous system. The observations are useful from the perspective of basic concepts of neural circuitry as well as a characterization of the pathways involved in pain and analgesia. Study of the spinal cord dorsal horn offers a unique advantage in that it contains many of the identified substances in the nervous system that act as neurotransmitters or neuromodulators (Table I). These neurochemicals include both classical neurotransmitters such as the monoamines and amino acids as well as recently discovered families of neuropeptides. This chapter seeks to address some of the fundamental observations on the anatomical and neurochemical organization of the dorsal horn and to apply the findings to basic issues of integration in the nervous system as well as to the study of pain and analgesia.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aronin, N., DiFiglia, M., Liotta, A. S., and Martin, J. B. Ultrastructural localization and biochemical features of immunoreactive leu-enkephalin in monkey dorsal horn. J. Neurosci. 1:561–577, 1981.
Barber, R. P., Vaughn, J. E., Sherman, J. R., Salvaterra, P. M., Roberts, E., and Leeman, S. E. The origin, distribution and synaptic relationships of substance P axons in rat spinal cord. J. Comp. Neurol. 184:331–352, 1979.
Basbaum, A. I. Anatomical substrates for the descending control of nociception, in: Brain Stem Control of Spinal Mechanisms (B. Sjöland and A. Björklund, eds.), Elsevier, Amsterdam, 1982, pp. 119–133.
Basbaum, A. I., Clanton, C. H., and Fields, H. L. Three bulbospinal pathways from the rostral medulla of the cat: An autoradiographic study of pain modulating systems. J. Comp. Neurol. 1:209–224, 1978.
Bennett, G. J., Abdelmoumene, M., Hayashi, H., and Dubner, R. Physiology and morphology of substantia gelatinosa neurons intracellularly stained with horseradish peroxidase. J. Comp. Neurol. 194:809–827, 1980.
Bennett, G. J., Abdelmoumene, M., Hayashi, H., Hoffert, M. J., and Dubner, R. Spinal cord layer I neurons with axon collaterals that generate local arbors. Brain Res. 209:421–426, 1981a.
Bennett, G. J., Abdelmoumene, M., Hayashi, H., Hoffert, M. J., Ruda, M. A., and Dubner, R. Physiology, morphology and immunocytology of dorsal horn layer III neurons. Pain [Suppl.] 1:S240, 1981b.
Bennett, G. J., Ruda, M. A., Gobel, S., and Dubner, R. Enkephalin immunoreactive stalked cells and lamina IIb islet cells in cat substantia gelatinosa. Brain Res. 240:162–166, 1982.
Bowker, R. M., Steinbusch, H. W. M., and Coulter, J. D. Serotonergic and peptidergic projections to the spinal cord demonstrated by a combined retrograde HRP histochemical and immunocytochemical staining method. Brain Res. 211:412–417, 1981a.
Bowker, R. M., Westlund, K. N., and Coulter, J. D. Origins of serotonergic projections to the spinal cord in rat: An immunocytochemical-retrograde transport study. Brain Res. 226:187–199, 1981b.
Burton, H., and Craig, A. D., Jr. Distribution of trigeminothalamic projection cells in cat and monkey. Brain Res. 161:515–521, 1979.
Carstens, F., and Trevino, D. L. Laminar origins of spinothalamic projections in the cat as determined by the retrograde transport of horseradish peroxidase. J. Comp. Neurol. 182:151–166, 1978.
Cuello, A. C., de LFiacco, M., and Paxinos, G. The central and peripheral ends of the substance P-containing sensory neurones in the rat trigeminal system. Brain Res. 152:499–509, 1978.
Dahlström, A., and Fuxe, K. Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol. Scand. [Suppl.] 232:1–55, 1964.
Dahlström, A., and Fuxe, K. Evidence for the existence of monoamine-containing neurons in the central nervous sytem. II. Experimentally induced changes in the intraneuronal amine levels of bulbospinal neuron systems. Acta Physiol. Scand. [Suppl] 247:7–36, 1965.
Delanerolle, N. C., and LaMotte, C. C. Ultrastructure of chemically denned neuron systems in the dorsal horn of the monkey. I. Substance P immunoreactivity. Brain Res. 274:31–49, 1983.
DiFiglia, M., Aronin, N., and Leeman, S. E. Light microscopic and ultrastructural localization of immunoreactive substance P in the dorsal horn of monkey spinal cord. Neuroscience 7:1127–1139, 1982.
Dubner, R., and Bennett, G. J. Spinal and trigeminal mechanisms of nociception. Annu. Rev. Neurosci. 6:381–418, 1983.
Dubner, R., Ruda, M. A., Miletic, V., Hoffert, M. J., Bennett, G. J., Nishikawa, N., and Coffield, J. Neural circuitry mediating nociception in the medullary and spinal dorsal horns, in: Advances in Pain Research and Therapy, Vol. 6 (L. Kruger and J. C. Liebeskind, eds.), Raven Press, New York, 1984, pp. 151–166.
Gibson, S. J., Polak, J. M., Bloom, S. R., and Wall, P. D. The distribution of nine peptides in rat spinal cord with special emphasis on the substantia gelatinosa and on the area around the central canal (lamina X). J. Comp. Neurol. 201:65–79, 1981.
Giesler, G. J., Jr., Menetrey, D., and Basbaum, A. I. Differential origins of spinothalamic tract projections to medial and lateral thalamus in the rat. J. Comp. Neurol. 184:107–126, 1979.
Giesler, G. J., Jr., Yezierski, R. P., Gerhart, K. D., and Willis, W. D. Spinothalamic tract neurons that project to medial and/or lateral thalamic nuclei: Evidence for a physiologically novel population of spinal cord neurons. J. Neurophysiol. 46:1285–1308, 1981.
Gilbert, R. F. T., Emson, P. C., Hunt, S. P., Bennett, G. W., Marsden, C. A., Sandberg, B. E. B., Steinbusch, H. W. M., and Verhofstad, A. A.J. Effects of monoamine neurotoxins on peptides in the rat spinal cord. Neuroscience 7:69–87, 1982.
Glazer, E. J., and Basbaum, A. I. Immunohistochemical localization of leucine-enkephalin in the spinal cord of the cat. Enkephalin-containing marginal neurons and pain modulation. J. Comp. Neurol. 196:377–389, 1981.
Glazer, E. J., and Basbaum, A. I. Opiate neurons and pain modulation: An ultrastructural analysis of enkephalin in cat superficial dorsal horn. Neuroscience 10:357–376, 1982.
Glazer, E. J., and Basbaum, A. I. Axons which take up [3H]serotonin are presynaptic to enkephalin immunoreactive neuron in cat dorsal horn. Brain Res. 298:386–391, 1984.
Hockfield, S., and Gobel, S. Neurons in and near nucleus caudalis with long ascending projection axons demonstrated by retrograde labeling with horseradish peroxidase. Brain Res. 139:333–339, 1978.
Hoffert, M. J., Miletic, V., Ruda, M. A., and Dubner, R. A comparison of substance P and serotonin axonal contacts on identified neurons in cat spinal dorsal horn. Soc. Neurosci. Abstr. 8:805, 1982.
Hoffert, M. J., Miletic, V., Ruda, M. A., and Dubner, R. Immunocytochemical identification of serotonin axonal contacts on characterized neurons in laminae I and II of the cat dorsal horn. Brain Res. 267:361–364, 1983.
Hökfelt, T., Kellerth, J. O., Nilsson, G., and Pernow, B. Substance P localization in the central nervous system and in some primary sensory neurons. Science 190:889–890, 1975a.
Hökfelt, T., Kellerth, J. O., Nilsson, G., and Pernow, B. Experimental immunohistochemical studies on the localization and distribution of substance P in the cat primary sensory neurons. Brain Res. 100:235–252, 1975b.
Hökfelt, T., Ljungdahl, A., Terenius, L., Elde, R., and Nilsson, G., Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: Enkephalin and substance P. Proc. Natl. Acad. Sci. U.S.A. 74:3081–3085, 1977.
Hökfelt, T., Terenius, L., Kuypers, H. G. J. M., and Dann, O. Evidence for enkephalin immunoreactive neurons in the medulla oblongata projecting to the spinal cord. Neurosci. Lett. 14:55–60, 1979.
Hunt, S. P., Kelly, J. S., and Emson, P. C. The electron microscopic localization of methionine-enkephalin within the superficial layers (I and II) of the spinal cord. Neuroscience 5:1871–1890, 1980.
Hunt, S. P., Kelly, J. S., Emson, P. C., Kimmel, J. R., Miller, R. J., and Wu, J. Y. An immunohistochemical study of neuronal populations containing neuropeptides or gamma-ami-nobutyrate within the superficial layers of the rat dorsal horn. Neuroscience 6:1883–1898, 1981.
Jessell, T., Tsunoo, A., Kanazawa, I., and Otsuka, M. 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, 1979.
Kenshalo, D. R., Jr., Leonard, R. B., Chung, J. M., and Willis, W. D. Responses of primate spinothalamic neurons to graded and to repeated noxious heat stimuli J. Neurophysiol. 42:1370–1389, 1979.
LaMotte, C. C., and Delanerolle, N. C. Ultrastructure of chemically defined neuron systems in the dorsal horn of the monkey. II. Methionine-enkephalin immunoreactivity. Brain Res. 274:51–63, 1983a.
LaMotte, C. C., and Delanerolle, N. C. Ultrastructure of chemically defined neuron systems in the dorsal horn of the monkey. III. Serotonin immunoreactivity. Brain Res. 274:65–77, 1983b.
Light, A. R., Trevino, D. L., and Perl, E. R. Morphological features of functionally defined neurons in the marginal zone and substantia gelatinosa of the spinal dorsal horn. J. Comp. Neurol. 186:151–171, 1979.
Light, A. R., Kavookjian, A. M., and Petrusz, P. The ultrastructure and synaptic connections of serotonin-immunoreactive terminals in spinal laminae I and II. Somatosens. Res. 1:33–50, 1983.
Ljungdahl, A., Hökfelt, T., and Nilsson, G. Distribution of substance P-immunoreactivity in the central nervous system of the rat. I. Cell bodies and nerve terminals. Neuroscience 3:861–943, 1978.
Massari, V. J., Tizabi, Y., Park, C. H., Moody, T. W., Helke, C. J., and O’donohue, T. L. Distribution and origin of bombesin, substance P and somatostatin in cat spinal cord. Peptides 4:673–681, 1983.
Miletic, V., Hoffert, M. J., Ruda, M. A., Dubner, R., and Shigenaga, Y. Serotonergic axonal contacts on identified cat spinal dorsal horn neurons and their correlation with nucleus raphe magnus stimulation. J. Comp. Neurol. 228:129–141, 1984.
Narotsky, R. A., and Kerr, F. W. L. Marginal neurons of the spinal cord: Types, afferent synaptology and functional considerations. Brain Res. 139:1–20, 1978.
Nishikawa, N., Bennett, G. J., Ruda, M. A., Lu, G.-W., and Dubner, R. Immunocytochemical evidence for a serotonergic innervation of dorsal column postsynaptic neurons in cat and monkey. Neuroscience 10:1333–1340, 1983.
Pickel, V. M., Reis, D. J., and Leeman, S. E. Ultrastructure of substance P in neurons of rat spinal cord. Brain Res. 122:534–540, 1977.
Price, D. D., Dubner, R., and Hu, J. W. Trigeminothalamic neurons in nucleus caudalis responsive to tactile, thermal, and nociceptive stimulation of monkey’s face. J. Neurophysiol. 39:936–953, 1976.
Price, D. D., Hayashi, H., Dubner, R., and Ruda, M. A. Functional relationships between neurons of marginal and substantia gelatinosa layers of primate dorsal horn. J. Neurophysiol. 42:1590–1608, 1979.
Priestley, J. V., Somogyi, P., and Cuello, A. C. Immunocytochemical localization of substance P in the trigeminal nucleus of the rat: A light and electron microscopic study. J. Comp. Neurol. 211:31–49, 1982.
Priestley, J. V., and Cuello, A. C. Substance P immunoreactive terminals in the spinal trigeminal nucleus synapse with lamina I neurons projecting to the thalamus, in: Substance P (P. Skraborek and D. Powell, eds.), Book Press, Dublin, 1983, pp. 251–252.
Ralston, H. J. III, and Ralston, D. D. The distribution of dorsal root axons in laminae I, II and III of the macaque spinal cord: A quantitative electron microscope study. J. Comp. Neurol 184:643–684, 1979.
Ruda, M. A. Opiates and pain pathways: Demonstration of enkephalin synapses on dorsal horn projection neurons. Science 215:1523–1525, 1982.
Ruda, M. A., Coffield, J., and Steinbusch, H. W. M. Immunocytochemical analysis of serotonergic axons in laminae I and II of the lumbar spinal cord of the cat. J. Neurosci. 2:1660–1671, 1982.
Ruda, M. A., Coffield, J., Bennett, G. J., and Dubner, R. Role of serotonin (5-HT) and enkephalin (ENK) in trigeminal and spinal pain pathways. J. Dent. Res. 62:691, 1983.
Ruda, M. A., and Coffield, J., Light and ultrastructural immunocytochemical localization of serotonin synapses on primate spinothalamic tract neurons. Soc. Neurosci. Abstr. 9:1, 1983.
Ruda, M. A., Coffield, J., and Dubner, R. Demonstration of postsynaptic opioid modulation of thalamic projection neurons by the combined techniques of retrograde horseradish peroxidase and enkephalin immunocytochemistry. J. Neurosci. 4:2117–2132, 1984.
Sar, M., Stumpf, W. E., Miller, R. J., Chang, K.J., and Cuatrecasas, P. Immunohistochemical localization of enkephalin in rat brain and spinal cord. J. Comp. Neurol. 182:17–38, 1978.
Seybold, V., and Elde, R. Immunohistochemical studies of peptidergic neurons in the dorsal horn of the spinal cord. J. Histochem. Cytochem. 28:367–370, 1980.
Steinbusch, H. W. M. Distribution of serotonin-immunoreactivity in the central nervous system of the rat—cell bodies and terminals. Neuroscience 6:557–618, 1981.
Sumal, K., K., Pickel, V. M., Miller, R. J., and Reis, D. J. Enkephalin-containing neurons in substantia gelatinosa of spinal trigeminal complex: Ultrastructure and synaptic interaction with primary sensory Afferents. Brain Res. 248:223–236, 1982.
Takahashi, T., and Otsuka, M. Regional distribution of substance P in the spinal cord and nerve roots of the cat and the effect of dorsal root section. Brain Res. 87:1–11, 1975.
Tessler, A., Himes, B. T., Artmyshyn, R., Murray, M., and Goldberger, M. E. Spinal neurons mediate return of substance P following deafferentation of cat spinal cord. Brain Res. 230:263–281, 1981.
Trevino, D. L., Maunz, R. A., Bryan, R. N., and Willis, W. D. Location of cells of origin of the spinothalamic tract in the lumbar enlargement of cat. Exp. Neurol. 34:64–77, 1972.
Uhl, G. R., Goodman, R. R., Kuhar, M. J., Children, S. R., and Snyder, S. H. Immunohistochemical mapping of enkephalin containing cell bodies, fibers and nerve terminals in the brain stem of the rat. Brain Res. 166:75–94, 1979.
Willcockson, W. S., Chung, J. M., Hori, Y., Lee, K. H., and Willis, W. D. Effects of ionto-phoretically released amino acids and amines on primate spinothalamic tract cells. J. Neurosci. 4:732–740, 1984a.
Willcockson, W. S., Chung, J. M., Hori, Y., Lee, K. H., and Willis, W. D. Effects of ionto-phoretically released peptides on primate spinothalamic tract cells. J. Neurosci. 4:741–750, 1984b.
Willis, W. D., Kenshalo, D. R., Jr, and Leonard, R. B. The cells of origin of the primate spinothalamic tract. J. Comp. Neurol. 188:543–574, 1979.
Willis, W. D., Trevino, D. L., Coulter, J. D., and Maunz, R. A. Responses to primate spinothalamic tract neurons to natural stimulation of hindlimb. J. Neurophysiol. 37:358–372, 1974.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1986 Springer Science+Business Media New York
About this chapter
Cite this chapter
Ruda, M.A. (1986). The Pattern and Place of Nociceptive Modulation in the Dorsal Horn. In: Yaksh, T.L. (eds) Spinal Afferent Processing. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4994-5_7
Download citation
DOI: https://doi.org/10.1007/978-1-4684-4994-5_7
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-4996-9
Online ISBN: 978-1-4684-4994-5
eBook Packages: Springer Book Archive