Skip to main content
SpringerLink
Log in

Transplantation Strategies for the Treatment of Pain

  • Chapter
Cell Transplantation for Neurological Disorders

Part of the book series: Contemporary Neuroscience ((CNEURO))

  • 77 Accesses

Abstract

The management of chronic pain syndromes presents a difficult challenge, and a recent release from the American Chronic Pain Association indicates that the problem is far from being resolved with currently available therapeutic regimens. Numerous neurosurgical, physiological, psychological, and pharmacologic approaches have been attempted (1), often with conflicting or disappointing outcomes in the long run. It has been estimated that 80% of all patients who consult physicians do so for pain problems, and nearly 100 million Americans suffer from some form of chronic pain. Included in this group are more than 8 million Americans who are permanently disabled by back pain, with 65,000 new cases/yr, and 30–50 million arthritics in the US, with 600,000 new cases/yr. Furthermore, some of the most severe chronic pain disorders are those associated with peripheral or central nerve lesions, estimated to include over one million Americans. Examples include trigeminal neuralgia, postherpetic neuralgia, phantom limb pain, causalgia, and spinal cord injuries. In addition, diabetic and alcoholic poly-neuropathies also cause a chronic neuropathic pain syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Fields, H. L. and Basbaum, A. I. (1990) Update on basic pain mechanisms. IASP Refresher Course on Pain Management, April 1.

    Google Scholar 

  2. Schmidt, W. K. (1997) An overview of current and investigational drugs for the treatment of chronic pain. Therapeutic Developments in Chronic Pain. National Managed Healthcare Conference, pp. 1–17.

    Google Scholar 

  3. Chaplan, S. R., Prgrel, J. W., and Yaksh, T. L. (1994) Role of voltage-dependent calcium channel subtypes in experimental tactile allodynia. J. Pharmacol. Exp. Ther. 269, 1117–1123.

    PubMed  CAS  Google Scholar 

  4. Brose, W. G., Cherukuir, S., Longton, W. C., Gaeta, R. R., and Presley, R. (1995) Safety and efficacy of SNX-111, a novel analgesic, in the management of intractable neuropathic and nociceptive pain in humans: preliminary results. Am. Pain Soc. Abstracts 14, A-116.

    Google Scholar 

  5. Hassenbusch, S. J., Pillay, P. K., Magdinec, M., et al. (1989) Constant infusion of morphine for intractable cancer pain using an implanted pump. J. Neurosurg. 73, 405–409.

    Google Scholar 

  6. Moulin, D. E. and Coyle, N. (1986) Spinal relief of cancer pain. Am. J. Nursing 86, 1050AA–1050BB.

    Google Scholar 

  7. Drasner, K., and Fields, H. F. (1988) Synergy between the antinociceptive effects of intrathecal clonidine and systemic morphine in the rat. Pain 32, 309–312.

    Article  PubMed  CAS  Google Scholar 

  8. Sherman, S. E., Loomis, C. W., Milne, B., et al. (1988) Intrathecal oxymetazoline produces analgesia via spinal a-adrenoceptors and potentiates spinal morphine. Eur. J. Pharmacol. 148, 371–380.

    Article  PubMed  CAS  Google Scholar 

  9. Wilcox, G. L., Carlsson, K.-H., Jochim, A., et al. (1987) Mutual potentiation of antinociceptive effects of morphine and clonidine on motor and sensory responses in rat spinal cord. Brain Res. 405, 84–93.

    Article  PubMed  CAS  Google Scholar 

  10. Yaksh, T. L. and Reddy, S. V. (1981) Studies in the primate on the analgetic effects associated with intrathecal actions of opiates, alpha-adrenergic agonists and baclofen. Anesthesiology 54, 451–467.

    Article  PubMed  CAS  Google Scholar 

  11. Unsicker, K. (1993) The trophic cocktail made by adrenal chromaffin cells. Exp. Neurol. 123, 167–173.

    Article  PubMed  CAS  Google Scholar 

  12. Carmichael, S. W. and Stoddard, S. L. (1993) The Adrenal Medulla: 1989–1991. CRC, Boca Raton, FL, p. 646.

    Google Scholar 

  13. Hama, A. T., Pappas, G. D., and Sagen, J. (1996) Adrenal medullary implants reduce transsynaptic degeneration in the spinal cord of rats following chronic constriction nerve injury. Exp. Neurol. 137, 81–93.

    Article  PubMed  CAS  Google Scholar 

  14. Hama, A. T., Unnerstall, J. R., Siegan, J., and Sagen, J. (1995) Modulation of altered NMDA receptor expression in rat spinal cord by peripheral nerve injury and adrenal medullary grafting. Brain Res, 687, 103–113.

    Article  PubMed  CAS  Google Scholar 

  15. Hama, A. T. and Sagen, J. (1994) Induction of spinal NADPH-diaphorase by nerve injury is attenuated by adrenal medullary transplants. Brain Res. 640, 345–351.

    Article  PubMed  CAS  Google Scholar 

  16. Siegan, J. B. and Sagen, J. (1995) Attenuation of NMDA-induced spinal hypersensitivity by adrenal medullary transplants. Brain Res. 680, 88–99.

    Article  PubMed  CAS  Google Scholar 

  17. Sagen, J., Pappas, G. D., and Perlow, M. J. (1986) Adrenal medullary tissue transplants in rat spinal cord reduce pain sensitivity. Brain Res. 384, 189–194.

    Article  PubMed  CAS  Google Scholar 

  18. Sagen, J., Wang, H., and Pappas, G. D. (1990) Adrenal medullary implants in the rat spinal cord reduce nociception in a chronic pain model. Pain 42, 69–79.

    Article  PubMed  CAS  Google Scholar 

  19. Sagen, J. (1996) Chromaffin cell transplants in the CNS: Basic and clinical update, in Yearbook of Cell and Tissue Transplantation 1996/1997 ( Lanza, R. P. and Chick, W. L., eds.), Kluwer, Netherlands.

    Google Scholar 

  20. Wang, H. and Sagen, J. (1994) Optimization of adrenal medullary allograft conditions for pain alleviation. J. Neural. Transplant Plastic 5, 49–64.

    Article  CAS  Google Scholar 

  21. Sagen, J. and Kemmler, J. E. (1989) Increased levels of met-enkephalin-like-immunoreactivity in the spinal cord CSF of rats with adrenal medullary transplants. Brain Res. 502, 1–10.

    Article  PubMed  CAS  Google Scholar 

  22. Sagen, J., Kemmler, J. E., and Wang, H. (1991) Adrenal medullary transplants increase spinal cerebrospinal fluid catecholamine levels and reduce pain sensitivity. J. Neurochem. 56, 623–627.

    Article  PubMed  CAS  Google Scholar 

  23. Björklund, A., Stenevi, U., Dunnett, S. B., and Gage, F. H. (1982) Cross-species grafting in a rat model of Parkinson’s disease. Nature 298, 652–654.

    Article  PubMed  Google Scholar 

  24. Brundin, P., Widner, H., Nilsson, O. G., Strecker, R. B., and Björklund, A. (1989) Intracerebral xenografts of dopamine neurons: The role of immunosuppression and the blood-brain barrier. Exp. Brain Res. 75, 197–207.

    Article  Google Scholar 

  25. Finsen, B., Pedersen, E. B., Sorensen, T., Hokland, M., and Zimmer, J. (1990) Immune reactions against intracerebral murine xenografts of fetal hippocampal tissue and cultured cortical astrocytes in the adult rat. Prog. Brain Res. 82, 111–128.

    Article  PubMed  CAS  Google Scholar 

  26. Mason, D. W., Charlton, H. M., Jones, A. J., Lavy, C. B. D., Puklavec, M., and Simmonds, S. J. (1986) The fate of allogeneic and xenogeneic neuronal tissue transplanted into the third ventricle of rodents. Neuroscience 19, 685–694.

    Article  PubMed  CAS  Google Scholar 

  27. Widner, H. and Brundin, P. (1988) Immunological aspects of grafting in the mammalian central nervous system. A review and speculative synthesis. Brain Res. Rev. 13, 287–324.

    Article  CAS  Google Scholar 

  28. Ortega, J., Sagen, J., and Pappas, G. D. (1992) Short-term immunosuppression enhances long-term survival of bovine chromaffin cell xenografts in rat CNS. Cell Transplant 1, 33–41.

    PubMed  CAS  Google Scholar 

  29. Schueler, S.B., Sagen, J., Pappas, G. D., and Kordower, J. H. (1995) Long-term viability of isolated bovine adrenal medullary chromaffin cells following intrastriatal transplantation. Cell Transplant 4, 55–64.

    Article  PubMed  CAS  Google Scholar 

  30. Schueler, S., Ortega, J., Sagen, J., and Korkower, J. (1993) Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: a novel hypothesis of adrenal graft viability. J. Neurosci. 13, 4496–4510.

    PubMed  CAS  Google Scholar 

  31. Czech, K., Pollak, R., Pappas, G. D., and Sagen, J. (1996) Bovine chromaffin cells for CNS transplantation do not elicit xenogeneic T cell proliferative responses in vitro. Cell Transplant 5, 257–267.

    Article  PubMed  CAS  Google Scholar 

  32. Sortwell, C. E., Petty, F., Kramer, G., and Sagen, J. (1994) In vivo release of catecholamines from xenogeneic chromaffin cell grafts with antidepressive activity. Exp. Neurol. 130, 1–8.

    Article  PubMed  CAS  Google Scholar 

  33. Ortega, J. and Sagen, J. (1993) Pharmacologic characterization of opioid peptide release from chromaffin cell transplants using brain slice superfusion method. Exp. Brain Res. 95, 381–387.

    Article  PubMed  CAS  Google Scholar 

  34. Sagen, J. and Ortega, J. (1994) Influence of the CNS environment on chromaffin cell survival and catecholamine secretion patterns. J. Neurochem. 63, 1159–1162.

    Article  PubMed  CAS  Google Scholar 

  35. Aebischer, P., Winn, S. R., and Galletti, P. M. (1988) Transplantation of neural tissue in polymer capsules. Brain Res. 448, 364–368.

    Article  PubMed  CAS  Google Scholar 

  36. Saitoh, Y., Taki, T., Arita, N., Ohnishi, T., and Hayakawa, T. (1995) Analgesia induced by transplantation of encapsulated tumor cells secreting 0-endorphin. J. Neurosurg. 82, 630–634.

    Article  PubMed  CAS  Google Scholar 

  37. Wu, H., McLoon, S. C., and Wilcox, G. (1993) Antinociception following implantation of mouse pituitary AtT-20 cells and genetically modified AtT-20/hEnk cells in rat spinal cord. J. Neural Transplant Plastic 4, 15–26.

    Article  CAS  Google Scholar 

  38. Wu, H., Wilcox, G., and McCloon, S. (1994) Implantation of AtT-20 or genetically modified AtT-20/hENK cells in mouse spinal cord induced antinociception and opioid tolerance. J. Neurosci. 14, 4806–4814.

    PubMed  CAS  Google Scholar 

  39. Saitoh, Y., Taki, T., Arita, N., Ohnishi, T., and Hayakawa, T. (1995) Cell therapy with encapsulated xenogeneic tumor cells secreting ß-endorphin for treatment of peripheral pain. Cell Transplant 4 (Suppl.), S13–S17.

    Google Scholar 

  40. Wu, H., Lester, B., Sun, Z., and Wilcox, G. (1994) Antinociception following implantation of mouse B16 melanoma cells in mouse and rat spinal cord. Pain 56, 203–210.

    Article  PubMed  CAS  Google Scholar 

  41. Eaton, M. J., Santiago, D. I., Dancausse, H. A., and Whittemore, S. R. (1997) Lumbar transplants of immortalized serotonergic neurons alleviate chronic neuropathic pain. Pain 72, 59–69.

    Article  PubMed  CAS  Google Scholar 

  42. Sagen, J., Pappas, GD., and Pollard, H. B. (1986) Analgesia induced by isolated bovine chromaffin cells implanted in rat spinal cord. Proc. Natl. Acad. Sci. USA 83, 7522–7526.

    Article  PubMed  CAS  Google Scholar 

  43. Sagen, J., Wang, H., Tresco, P., and Aebischer, P. (1993) Transplants of immunologically isolated xenogeneic chromaffin cells provide a long-term source of pain-reducing neuroactive substances. J. Neurosci. 13, 2415–2423.

    PubMed  CAS  Google Scholar 

  44. Ortega-Alvaro, A., Gibert-Rahola, J., Choyer, A. J., Tejedor-Real, P., Casas, J., and Mico, A. (1994) Effect of amitriptyline on the analgesia induced by adrenal medullary tissue transplanted in the rat spinal subarachnoid space. Exp. Neurol. 130, 9–14.

    Article  PubMed  CAS  Google Scholar 

  45. Ruz-Franzi, J. I. and Gonzalez-Darder, J. M. (1991) Study of the analgesic effects of the implant of adrenal medulla into the subarachnoid space in rats. Acta Neurochir. 52, 39–41.

    Article  CAS  Google Scholar 

  46. Pacheco-Cano, M. T., Garcia-Hernandez, F., Hiriart, M., Komisaruk, B. R., and Drucker-Colin, R. (1990) Dibutyryl cAMP stimulates analgesia in rats bearing a ventricular adrenal medulla transplant. Brain Res. 531, 290–293.

    Article  PubMed  CAS  Google Scholar 

  47. Coderre, T. J. and Yashpal, K. (1994) Intracellular messengers contributing to persistent nociception and hyperalgesia induced by L-glutamate and substance P in the rat formalin pain model. Eur. J. Neurosci. 6, 1328–1334.

    Article  PubMed  CAS  Google Scholar 

  48. Hunter, J. C. and Singh, L. (1994) Role of excitatory amino acid receptors in the mediation of the nociceptive response to formalin in the rat. Neurosci. Lett. 174 217–221.

    Google Scholar 

  49. Yamamoto, T. and Yaksh, T. L. (1992) Comparison of the antinociceptive effects of pre-and posttreatment with intrathecal morphine and MK801, an NMDA antagonist, on the formalin test in the rat. Anesthesiology 77, 757–763.

    Article  PubMed  CAS  Google Scholar 

  50. Siegan, J. and Sagen, J. (1997) Attentuation of formalin pain responses in the rat by adrenal medullary transplants in the spinal subarachnoid space. Pain 70, 279–285.

    Article  PubMed  CAS  Google Scholar 

  51. Vaquero, J., Arias, A., Oya, S., and Zurita, M. (1991) Chromaffin allografts into arachnoid of spinal cord reduce basal pain responses in rats. NeuroReport 2, 149–151.

    Article  PubMed  CAS  Google Scholar 

  52. Calvino, B., Crepon-Bernard, M.-O., and Le Bars, D. (1987) Parallel clinical and behavioural studies of adjuvant-induced arthritis in the rat: possible relationship with “chronic pain.” Behay. Brain Res. 24, 11–29.

    Article  CAS  Google Scholar 

  53. Colpaert, F. C. (1987) Evidence that adjuvant arthritis in the rat is associated with chronic pain. Pain 28, 201–222.

    Article  PubMed  CAS  Google Scholar 

  54. Dardick, S. J., Basbaum, A. I., and Levine, J. D. (1986) The contribution of pain to disability in experimentally induced arthritis. Arthritis Rheum. 29, 1017–1022.

    Article  PubMed  CAS  Google Scholar 

  55. De Castro Costa, M., De Sutter, P., Gybels, J., and Van Hess, J. (1981) Adjuvant-induced arthritis in rats: a possible animal model of chronic pain. Pain 10, 173–185.

    Article  PubMed  Google Scholar 

  56. Glynn, C. J., Lloyd, J. W., and Olkhard, S. (1981) Ventilatory response to intractable pain. Pain 11, 201–211.

    Google Scholar 

  57. Wang, H. and Sagen, J. (1995) Attenuation of pain-related hyperventilation in adjuvant arthritic rats with adrenal medullary transplants in the spinal subarachnoid space. Pain 63, 313–320.

    Article  PubMed  CAS  Google Scholar 

  58. Colpaert, F. C., Bervoets, K. J. W., and Van den Hoogen, R. H. W. M. (1983) Pharmacological analysis of hyperventilation in arthritic rats. Pain 30, 243–258.

    Article  Google Scholar 

  59. Colpaert, F. C. and Van den Hoogen, R. H. W. M. (1983) Time course of the ventilatory response to adjuvant arthritis in the rat. Life Sci. 33, 1065–1073.

    Article  PubMed  CAS  Google Scholar 

  60. Bennett, G. J. and Xie, Y.-K. (1988) A peripheral mononeuropathy in rats that produces disorders of pain sensation like those seen in human. Pain 33, 87–107.

    Google Scholar 

  61. Hama, A. T. and Sagen, J. (1993) Reduced pain-related behavior by adrenal medullary transplants in rats with experimental painful peripheral neuropathy. Pain 53, 223–231.

    Article  Google Scholar 

  62. Hama, A. T. and Sagen, J. (1994) Alleviation of neuropathic pain symptoms by xenogeneic chromaffin cell grafts in the spinal subarachnoid space. Brain Res. 651, 183–193.

    Article  PubMed  CAS  Google Scholar 

  63. Sagen, J., Hama, A. T., Winn, S. R., Tresco, P. A., and Aebischer, P. (1993) Pain reduction by spinal implantation of xenogeneic chromaffin cells immunologically-isolated in polymer capsules. Soc. Neurosci. Abstracts 19, 234.

    Google Scholar 

  64. Ginzburg, R. and Seltzer, Z. (1990) Subarachnoid spinal cord transplantation of adrenal medulla suppresses chronic neuropathic pain behavior in rats. Brain Res. 523, 147–150.

    Article  PubMed  CAS  Google Scholar 

  65. Yu, W., Hao, J.-X., Xu, X.-J., Saydoff, J., Haegerstrand, A., and Wiesenfeld-Hallin, Z. (1996) Intrathecal bovine chromaffin cells alleviate chronic allodynia-like response in spinally injured rats. IASP Abstracts,in press.

    Google Scholar 

  66. Wang, H. and Sagen, J. (1994) Absence of appreciable tolerance and morphine cross-tolerance in rats with adrenal medullary transplants in the spinal cord. Neuropharmacology 33, 681–692.

    Article  PubMed  CAS  Google Scholar 

  67. Winnie, A., Pappas, G. D., Gupta, T. K., Wang, H., Ortega, J., and Sagen, J. (1993) Subarachnoid adrenal medullary transplants for terminal cancer pain. Anesthesiology 79, 644–653.

    Article  PubMed  CAS  Google Scholar 

  68. Lazorthes, Y., Bes, J. C., Sagen, J., Tafani, M., Tkaczuk, J., Sallerin, B., et al. (1996) Transplantation of human chromaffin cells for intractable cancer pain control. Acta Neurochir. 64, 97–100.

    Article  Google Scholar 

  69. Vaquero, J., Martinez, R., Oya, S., Coca!, S., Salazar, F. G., and Colado, M. I. (1988) Transplantation of adrenal medulla into spinal cord for pain relief: disappointing outcome. Lancet 12/3, 1315.

    Google Scholar 

  70. Drucker-Colin, R., Madrazo, I., Ostrosky-Solis, F., Shkurovich, M., Franco, R., and Torres, C. (1988) Adrenal medullary tissue transplants in the caudate nucleus of Parkinson’s patients, in Transplantation in the Mammalain CNS (Gash, D. M. and Sladek, J. R., Jr., eds.), Elsevier, Amsterdam, Prog. Brain Res. 78, 567–574.

    Google Scholar 

  71. Penn, R. D., Goetz, D. G., Tanner, C. M., Klawans, H. L., Shannon, K. M., Comella, C. L., et al. (1988) The adrenal medullary transplant ooperation for Parkinson’s disease: clinical observations in five patients. Neurosurgery 22, 999–1004.

    Article  PubMed  CAS  Google Scholar 

  72. Aebischer, P., Buscher, E., Joseph, J. M., Favre, J., de Tribolet, N., Lysaght, M., et al. (1994) Transplantation in humans of encapsulated xenogeneic cells without immunosuppression: a preliminary report. Transplantation 58, 1–3.

    Article  Google Scholar 

  73. Buscher, E., Goddard, M., Heyd, B., Joseph, J. M., Favre, J., de Tribolet, N., et al. (1996) Immunoisolated xenogeneic chromaffin cell therapy for chronic pain: initial clinical experience. Anesthesiology 85, 1005–1012.

    Article  Google Scholar 

  74. Joseph, J. M., Goddard, M. B., Mills, J., Padrun, V., Zum, A., Zeilinski, B., et al. (1994) Transplantation of encapsulated bovine chromaffin cells in the sheep subarachnoid space: a preclinical study for the treatment of cancer pain. Cell Transplant 3, 355–364.

    PubMed  CAS  Google Scholar 

  75. Burgess, F. W., Goddard, M., Savarese, D., and Wilkonson, H. (1996) Subarachnoid bovine adrenal chromaffin cell implants for cancer pain management. Am. Pain Soc. Abstr. 15, A33.

    Google Scholar 

Download references

Authors
  1. Jacqueline Sagen
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Neurosurgery, Department of Pharmacology and Experimental Therapeutics, The Neuroscience Program, University of South Florida, Tampa, FL, USA

    Thomas B. Freeman MD

  2. Departments of Clinical Neurosciences and Physiology and Neuroscience, Wallenberg Neuroscience Center, Lund University, Lund, Sweden

    Håkan Widner MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Sagen, J. (1998). Transplantation Strategies for the Treatment of Pain. In: Freeman, T.B., Widner, H. (eds) Cell Transplantation for Neurological Disorders. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-476-4_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-476-4_12

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-043-4

  • Online ISBN: 978-1-59259-476-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation