, Volume 38, Issue 5–6, pp 410–420 | Cite as

The spinal cord in vitro: What can it tell us about nociception?

  • A. E. King
Proceeding of The International Workshop “The Study of Nociception from Periphery to Brainstem” (June 4–7, 2006, Kyiv)


The use of amphibian and mammalian in vitro spinal cord preparations, e.g., hemisected cord and transverse slices, has gained in popularity over the years due to the flexibility and ease of use of such preparations compared to classical in vivo approaches. When combined with modern experimental methodologies, such as patch clamping of visualized single cells or post-experimental neuroanatomy, this approach provides a powerful addition to the armamentarium available to study nociceptive processing in the dorsal horn. Some of these novel experimental approaches and the insight into nociception that they have provided are described below.


dorsal horn in vitro spinal cord nociception pain neuronal networks 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Y. Kudo, “The pharmacology of the amphibian spinal cord,” Prog. Neurobiol., 11, 1–76 (1978).PubMedCrossRefGoogle Scholar
  2. 2.
    C. L. Li and H. McIlwain, “Maintenance of resting membrane potentials in slices of mammalian cerebral cortex and other tissues in vitro,” J. Physiol, 139, 178–190 (1957).PubMedGoogle Scholar
  3. 3.
    M. Otsuka and S. Konishi, “Electrophysiology of mammalian spinal cord in vitro,” Nature, 252, 733–734 (1974).PubMedCrossRefGoogle Scholar
  4. 4.
    M. Otsuka, S. Konishi, T. Takahashi, and K. Saito, “Substance P and primary afferent transmission,” Adv. Biochem. Psychopharmacol., 15, 187–191 (1976).PubMedGoogle Scholar
  5. 5.
    A. I. Shapovalov, B. I. Shiriaev, and Z. A. Tamarova, “Synaptic activity in motoneurons of the immature cat spinal cord in vitro. Effects of manganese and tetrodotoxin,” Brain Res., 160, 524–528, (1979).PubMedCrossRefGoogle Scholar
  6. 6.
    Z. A. Tamarova, A. I. Shapovalov, and B. I. Shiriaev, “Effect of magnesium, manganese ions and calcium deficiency on synaptic transmission in isolated rat spinal cord,” Neirofiziologiya., 10, 530–533 (1978).Google Scholar
  7. 7.
    G. A. Kerkut and J. Bagust, “The isolated mammalian spinal cord,” Prog. Neurobiol., 46, 1–48 (1995).PubMedCrossRefGoogle Scholar
  8. 8.
    R. H. Evans, “The pharmacology of segmental transmission in the spinal cord,” Prog. Neurobiol., 33, 255–279 (1989).PubMedCrossRefGoogle Scholar
  9. 9.
    A. E. King, J. R. Slack, J. A. Lopez-Garcia, and M. A. Ackley, “Tachykinin actions on deep dorsal horn neurons in vitro: an electrophysiological and morphological study in the immature rat,” Eur. J. Neurosci., 9, 1037–1046 (1997).PubMedCrossRefGoogle Scholar
  10. 10.
    A. E. King and X. H. Liu, “Dual action of metabotropic glutamate receptor agonists on neuronal excitability and synaptic transmission in spinal central horn neurons in vitro,” Neuropharmacology, 35, 1673–1680 (1996).PubMedCrossRefGoogle Scholar
  11. 11.
    J. A. Lopez-Garcia and A. E. King, “Pre-and postsynaptic actions of 5-hydroxytryptamine in the rat lumbar dorsal horn in vitro: Implications for somatosensory transmission,” Eur. J. Neurosci., 8, 2188–2197 (1996).PubMedCrossRefGoogle Scholar
  12. 12.
    S. G. Khasabov, J. A. Lopez-Garcia, and A. E. King, “Serotonin-induced population primary afferent depolarization in vitro: the effects of neonatal capsaicin treatment,” Brain Res., 789, 339–342 (1998).PubMedCrossRefGoogle Scholar
  13. 13.
    S. W. N. Thompson, A. E. King, and C. J. Woolf, “Activity-dependent changes in rat ventral horn neurones in vitro; summation of prolonged afferent-evoked postsynaptic depolarizations produce a d-APV sensitive windup,” Eur. J. Neurosci., 2, 638–649 (1990).PubMedCrossRefGoogle Scholar
  14. 14.
    A. U. Asghar, S. S. Hasan, and A. E. King, “The anticonvulsant remacemide and its metabolite ARR12495AA attenuate spinal synaptic transmission and carrageenan-induced inflammation in the young rat,” Eur. J. Pain, 4, 97–106 (2000).PubMedCrossRefGoogle Scholar
  15. 15.
    M. Fitzgerald, A. E. King, S. W. Thompson, and C. J. Woolf, “The postnatal development of the ventral root reflex in the rat; a comparative in vivo and in vitro study,” Neurosci. Lett., 78, 41–45 (1987).PubMedCrossRefGoogle Scholar
  16. 16.
    S. K. Long, R. H. Evans, L. Cull, et al., “An in vitro mature spinal cord preparation from the rat,” Neuropharmacology, 27, 541–546 (1988).PubMedCrossRefGoogle Scholar
  17. 17.
    H. Badie-Mahdavi, M. A. Worsley, M. A. Ackley, et al., “A role for protein kinase intracellular messengers in substance P-and nociceptor afferent-mediated excitation and expression of the transcription factor Fos in rat dorsal horn neurons in vitro,” Eur. J. Neurosci., 14, 426–434 (2001).PubMedCrossRefGoogle Scholar
  18. 18.
    R. Bardoni, P. C. Magherini, and A. B. MacDermott, “NMDA EPSCs at glutamatergic synapses in the spinal cord dorsal horn of the postnatal rat,” J. Neurosci., 18, 6558–6567 (1998).PubMedGoogle Scholar
  19. 19.
    G. N. Bentley and J. P. Gent, “Neurokinin actions on substantia gelatinosa neurones in an adult longitudinal spinal cord preparation,” Brain Res., 673, 101–111 (1995).PubMedCrossRefGoogle Scholar
  20. 20.
    A. W. Hantman, A. N. Van den Pol, and E. R. Perl, “Morphological and physiological features of a set of spinal substantia gelatinosa neurons defined by green fluorescent protein expression,” J. Neurosci., 24, 836–842 (2004).PubMedCrossRefGoogle Scholar
  21. 21.
    T. Ataka, E. Kumamoto, K. Shimoji, and M. Yoshimura, “Baclofen inhibits more effectively C-afferent than Aδ-afferent glutamatergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices,” Pain, 86, 273–282 (2000).PubMedCrossRefGoogle Scholar
  22. 22.
    M. A. Ackley, R. J. Governo, C. E. Cass, et al., “Control of glutamatergic neurotransmission in the rat spinal dorsal horn by the nucleoside transporter ENT1,” J. Physiol., 548, 507–517 (2003).PubMedCrossRefGoogle Scholar
  23. 23.
    R. J. Governo, J. Deuchars, S. A. Baldwin, and A. E. King, “Localization of the NBMPR-sensitive equilibrative nucleoside transporter, ENT1, in the rat dorsal root ganglion and lumbar spinal cord,” Brain Res., 1059, 129–138 (2005).PubMedCrossRefGoogle Scholar
  24. 24.
    M. A. Ackley, S. A. Baldwin, and A. E. King, “Adenosine contributes to mu-opioid synaptic inhibition in rat substantia gelatinosa in vitro,” Neurosci. Lett., 376, 102–106 (2005).PubMedCrossRefGoogle Scholar
  25. 25.
    G. C. Bird, A. U. Asghar, M. A. Ackley, and A. E. King, “Modulation of primary afferent-mediated neurotransmission and Fos expression by glutamate uptake inhibition in rat spinal neurones in vitro,” Neuropharmacology, 41, 582–591 (2001).PubMedCrossRefGoogle Scholar
  26. 26.
    A. U. Asghar, P. F. Cilia La Corte, F. E. LeBeau, et al., “Oscillatory activity within rat substantia gelatinosa in vitro: a role for chemical and electrical neurotransmission,” J. Physiol, 562, 183–198 (2005).PubMedCrossRefGoogle Scholar
  27. 27.
    J. Sandkuhler, A. Eblen-Zajjur, Q. G. Fu, and C. Forster, “Differential effects of spinalization on discharge patterns and discharge rates of simultaneously recorded nociceptive and non-nociceptive spinal dorsal horn neurons,” Pain, 60, 55–65 (1995).PubMedCrossRefGoogle Scholar
  28. 28.
    A. A. Eblen-Zajjur and J. Sandkuhler, “Synchronicity of nociceptive and non-nociceptive adjacent neurons in the spinal dorsal horn of the rat: Stimulus-induced plasticity,” Neuroscience, 76, 39–54 (1997).PubMedCrossRefGoogle Scholar
  29. 29.
    K. J. Hilton, A. N. Bateson, and A. E. King, “A model of organotypic rat spinal slice culture and biolistic transfection to elucidate factors that drive the preprotachykinin-A promoter,” Brain Res. Brain Res. Rev., 46, 191–203 (2004).PubMedCrossRefGoogle Scholar
  30. 30.
    K. J. Hilton, A. N. Bateson, and A. E. King, “Neurotrophin-induced preprotachykinin-A gene promoter modulation in organotypic rat spinal cord culture,” J. Neurochem., 98, 690–699 (2006).PubMedCrossRefGoogle Scholar
  31. 31.
    K. Noguchi and M. A. Ruda, “Gene regulation in an ascending nociceptive pathway: inflammation-induced increase in preprotachykinin mRNA in rat lamina I spinal projection neurons,” J. Neurosci., 12, 2563–2572 (1992).PubMedGoogle Scholar
  32. 32.
    I. Kangrga and M. Randic, “Outflow of endogenous aspartate and glutamate from the rat spinal dorsal horn in vitro by activation of low-and high-threshold primary afferent fibers. Modulation by mu-opioids,” Brain Res., 553, 347–352 (1991).PubMedCrossRefGoogle Scholar
  33. 33.
    M. Otsuka and M. Yanagisawa, “Effect of a tachykinin antagonist on a nociceptive reflex in the isolated spinal cord-tail preparation of the newborn rat,” J. Physiol., 395, 255–270 (1988).PubMedGoogle Scholar
  34. 34.
    A. Rueff and A. Dray, “Sensitization of peripheral afferent fibres in the in vitro neonatal rat spinal cord-tail by bradykinin and prostaglandins,” Neuroscience, 54, 527–535 (1993).PubMedCrossRefGoogle Scholar
  35. 35.
    S. P. Schneider and E. R. Perl, “Synaptic mediation from cutaneous mechanical nociceptors,” J. Neurophysiol., 72, 612–621 (1994).PubMedGoogle Scholar
  36. 36.
    E. Sykova, G. Czeh, and N. Kriz, “Potassium accumulation in the frog spinal cord induced by nociceptive stimulation of the skin,” Neurosci. Lett., 17, 253–258 (1980).PubMedCrossRefGoogle Scholar
  37. 37.
    N. Kudo and T. Yamada, “N-methyl-D,L-aspartate-induced locomotor activity in a spinal cord-hindlimb muscles preparation of the newborn rat studied in vitro,” Neurosci. Lett., 75, 43–48 (1987).PubMedCrossRefGoogle Scholar
  38. 38.
    B. A. Chizh, P. M. Headley, and J. F. R. Paton, “An arterially-perfused trunk-hindquarters preparation of adult mouse in vitro,” J. Neurosci. Methods, 76, 177–182 (1997).PubMedCrossRefGoogle Scholar
  39. 39.
    A. E. King and J. A. Lopez-Garcia, “Excitatory amino acid receptor-mediated neurotransmission from cutaneous afferents in rat dorsal horn in vitro,” J. Physiol., 472, 443–457 (1993).PubMedGoogle Scholar
  40. 40.
    A. E. King, S. W. Thompson, and C. J. Woolf, “Characterization of the cutaneous input to the ventral horn in vitro using the isolated spinal cord-hind limb preparation,” J. Neurosci. Methods, 35, 39–46 (1990).PubMedCrossRefGoogle Scholar
  41. 41.
    J. A. Lopez-Garcia and A. E. King, “Membrane properties of physiologically classified rat dorsal horn neurones in vitro: correlation with cutaneous sensory afferent input,” Eur. J. Neurosci., 6, 998–1007 (1994).PubMedCrossRefGoogle Scholar
  42. 42.
    A. E. King and J. A. Lopez-Garcia, “Intracellular analysis of cutaneous afferent-induced excitation and inhibition in rat dorsal horn neurones in vitro,” J. Neurosci. Methods, 52, 61–68 (1994).PubMedCrossRefGoogle Scholar
  43. 43.
    J. S. Mogil and K. E. McCarson, “Identifying pain genes: bottom-up and top-down approaches,” J. Pain, 1, 66–80 (2000).PubMedCrossRefGoogle Scholar
  44. 44.
    B. Heinke, R. Ruscheweyh, L. Forsthuber, et al., “Physiological, neurochemical and morphological properties of a subgroup of GABAergic spinal lamina II neurones identified by expression of green fluorescent protein in mice,” J. Physiol., 560, 249–266 (2004).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Institute of Membrane and Systems BiologyUniversity of LeedsLeedsUK

Personalised recommendations