Skip to main content

Proinflammatory cytokines and glial cells: Their role in neuropathic pain

  • Chapter
Book cover Cytokines and Pain

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

Neuropathic pain, or chronic pain due to nerve injury, is a prevalent condition for which currently there is no effective treatment. These neuropathic pain syndromes include deafferentation pain, diabetic, cancer and ischemic neuropathies, phantom limb pain, trigeminal neuralgia, postherpetic neuralgias and nerve injury caused by surgery or trauma [1]. Neuropathic pain is not only chronic and intractable, it is debilitating and causes extreme physical, psychological and social distress. In an effort to provide even temporary relief, narcotics (opioids) are often used inappropriately and in excess. Even if opioids provide some initial relief, tolerance and physical dependence are major limitations to their continued use. Clearly, development of non-opioid and non-addictive treatments for neuropathic pain would offer tremendous benefit to chronic pain patients. Our laboratory has focused on understanding mechanisms that lead to neuropathic pain. This knowledge may then translate into development of new, effective approaches for treatment and even prevention of chronic pain syndromes.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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. Loeser JD. (1990) Peripheral nerve disorders (peripheral neuropathies). In: Bonica J (ed): The management of pain,. 2nd ed. Lea and Febiger, Pennsylvania, 211–219

    Google Scholar 

  2. DeLeo JA, Coombs DW (1991) Autotomy and decreased substance P following peripheral cryogenic nerve lesion. Cryobiol 28: 460–466

    Article  CAS  Google Scholar 

  3. DeLeo JA, Coombs DW, Willenbring SW, Colburn RW, Fromm C, Wagner R, Twitchell BB (1994) Characterization of a neuropathic pain model: Sciatic cryoneurolysis in the rat. Pain 56: 9–16.

    Article  PubMed  CAS  Google Scholar 

  4. Willenbring S, DeLeo JA, Coombs DW (19 94) Differential behavioral outcomes in the sciatic cryoneurolysis model of neuropathic pain in rats. Pain 58: 135–140

    Article  PubMed  CAS  Google Scholar 

  5. Colburn RW, DeLeo JA, Rickman AJ, Yeager MP, Kwon P, Hickey WF (1997) Dissociation of microglial activation and neuropathic pain behaviors following peripheral nerve injury in the rat. J Neuroimmunol 79: 163–175

    Article  PubMed  CAS  Google Scholar 

  6. Colburn RW, DeLeo JA, Rickman AJ (1997) The effect of site vs. type of nerve injury on glial activation, spinal cytokine expression and behavior in the rat. Soc for Neurosci Abstr, New Orleans, LA

    Google Scholar 

  7. Bennett GJ, Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33: 87–107

    Article  PubMed  CAS  Google Scholar 

  8. Kim SH, Chung JM (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50: 355–363

    Article  PubMed  CAS  Google Scholar 

  9. Woolf CJ, Allchorne A, Safieh-Garabedian B, Poole S (1997) Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor-a. Brit J Pharm 121: 417–424

    Article  CAS  Google Scholar 

  10. Rothwell NJ (1991) Functions and mechanisms of interleukin-1 in the brain. Trends Pharmacol Sci 12: 430–436

    Article  PubMed  CAS  Google Scholar 

  11. Fontana A, Kristensen F, Dubs R, Gemsa D, Weber E (1992) Production of Joyce A. DeLeo and Raymond W. Colburn prostaglandin E and an interleukin-1 like factor by cultured astrocytes and C6 glioma cells. J Immunol 129: 2413–2419

    Google Scholar 

  12. Giulian D, Baker TJ, Shih L-CN, Lachman LB (1986) Interleukin-1 of the central nervous system is produced by ameboid microglia. J Exp Med 164: 594–604

    Article  PubMed  CAS  Google Scholar 

  13. Farrar WL, Hill JM, Harel-Bellan A, Vinocour M (1987) The immunological brain. Immunol Rev 100: 361–378

    Article  PubMed  CAS  Google Scholar 

  14. Lechan RM, Toni R, Clark BD, Cannon JG, Shaw AR, Dinarello CA, Reichlin S (1990) Immunoreactive interleukin-1(3 localization in the rat forebrain. Brain Res 514: 135–140

    Article  PubMed  CAS  Google Scholar 

  15. Sheeran P, Hall GM (1997) Cytokines in anaesthesia. Brit J Anaes 78: 201–219

    Article  CAS  Google Scholar 

  16. Rotshenker S, Aamar S, and Barak V (1992) Interleukin-1 activity in lesioned peripheral nerve. J Neuroimmunol 39: 75–80

    Article  PubMed  CAS  Google Scholar 

  17. Watkins LR, Wiertelak EP, Goehler LE, Smith KP, Martin D, Maier SF (1994) Characterization of cytokine-induced hyperalgesia. Brain Res 654: 15–26

    Article  PubMed  CAS  Google Scholar 

  18. Oka T, Aou S, Hori T (1993) Intracerebroventricular injection of interleukin-1(3 induces hyperalgesia in rats. Brain Res 624: 61–68

    Article  PubMed  CAS  Google Scholar 

  19. Oka T, Aou S, Hori T (1994) Intracerebroventricular injection of interleukin-113 enhances nociceptive neuronal responses of trigeminal nucleus caudalis in rats. Brain Res 656: 236–244

    Article  PubMed  CAS  Google Scholar 

  20. Oka T, Oka K, Hosoi M, Aou S, Hori T (1995) The opposing effects of interleukin-113 microinjected into the preoptic hypothalamus on nociceptive behavior in rats. Brain Res 700: 271–278

    Article  PubMed  CAS  Google Scholar 

  21. Won C, Park HJ, Shin HC (1995) Interleukin-113 facilitates afferent sensory transmission in the primary somatosensory cortex of anesthestized rats. Neurosci Letters 201: 255–258

    Article  CAS  Google Scholar 

  22. Patterson PH, Nawa H (1993) Neuronal differentiation factors/cytokines and synaptic plasticity. Cell 72: 123–137

    Article  PubMed  Google Scholar 

  23. Taga T (1996) gp130, a shared signal transducing receptor component for hematopoietic and neuropoietic cytokines. J Neurochem 67: 1–10

    Article  PubMed  CAS  Google Scholar 

  24. Kiefer R, Lindholm, D, Kreutzberg, G (1993) Interleukin-6 and transforming growth factor-131 mRNAs are induced in rat facial nucleus following motorneuron axotomy. Eur J Neurosci 5: 775–781

    Article  PubMed  CAS  Google Scholar 

  25. Murphy PG, Grodin J, Altares M, Richardson PM (1995) Induction of interleukin-6 in axotomized sensory neurons. J Neurosci 15: 5130–5138

    PubMed  CAS  Google Scholar 

  26. Bolin LM, Verity AN, Silver JE, Shooter EM, Abrams JS (1995) Interleukin-6 production in schwann cells and induction in sciatic nerve injury. J Neurochem 64: 850–858

    Article  PubMed  CAS  Google Scholar 

  27. Frei K, Malipiero UV, Leist TP, Zinkernagel RM, Schwab ME, Fontana A (1989) On the cellular source and function of interleukin-6 produced by the central nervous system. Eur J Immunol 19: 689–694

    Article  PubMed  CAS  Google Scholar 

  28. Le J, Vilcek J (1989) Interleukin-6: a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab Invest 61: 588–602

    PubMed  CAS  Google Scholar 

  29. Fattori E, Lazzaro D, Musiani P, Modesti A, Alonzi T, Ciliberto G (1995) IL-6 expres-sion in neurons of transgenic mice causes reactive astrocytosis and increase ramified microglial cells but no neuronal damage. Eur J Neurosci 7: 2441–2449

    Article  PubMed  CAS  Google Scholar 

  30. DeLeo JA and RW Colburn (1996) The role of cytokines in nociception and chronic pain. In: Weinstein J, Gordon S (eds): Low back pain: A scientific and clinical overview. American Academy of Orthopaedic Surgeons, Illinois, 163–186

    Google Scholar 

  31. Oka T, Oka K, Hosoi M, Hori T (1995) Intracerebroventricular injection of interleukin6 induces thermal hyperalgesia in rats. Brain Res 692: 123–128

    Article  PubMed  CAS  Google Scholar 

  32. DeLeo JA, Colburn RW, Nichols M, Malhotra A (1996) Interleukin (IL)-6 mediated hyperalgesia/alloydnia and increased spinal IL-6 in a mononeuropathy model in the rat. J Interferon and Cytokine Res 16: 695–700

    Article  CAS  Google Scholar 

  33. Qui Z, Parson KL, Gruol DL (1995) Interleukin-6 selectively enhances the intracellular calcium response to NMDA in developing CNS neurons. J Neurosci 15: 6688–6699

    Google Scholar 

  34. Meller ST, Gebhart GF (1993) Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain 52: 127–136

    Article  PubMed  CAS  Google Scholar 

  35. Davar G, Jama A, Deykin A, Vos B, Maciewicz R (1991) MK-801 blocks the development of thermal hyperalgesia in a rat model of experimental painful neuropathy. Brain Res 553: 327–330

    Article  PubMed  CAS  Google Scholar 

  36. Price DD, Mao J, Frenk H, Mayer DJ (1994) The N-methyl-D-aspartate receptor antagonist dextromethorphan selectively reduces temporal summation of second pain in man. Pain 59: 165–174.

    Article  PubMed  CAS  Google Scholar 

  37. Beutler B, Greenwald D, Hulmes JD, Chang M, Pan YC, Mathison J, Ulevitch R, Cera-mi A (1985) Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature 316: 552–554

    Article  PubMed  CAS  Google Scholar 

  38. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) An endotoxininduced serum factor that causes necrosis of tumors. Proc Natl Acad Sci 72: 3666–3669

    Article  PubMed  CAS  Google Scholar 

  39. Tsujimoto M, Vilcek J (1986) Tumor necrosis factor receptors in HeLa cells and their regulation by interferon-gamma. J Biol Chem 261: 5384–5388

    PubMed  CAS  Google Scholar 

  40. Smith CA, Davis T, Anderson D (1990) A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science 248: 1019–1023

    Article  PubMed  CAS  Google Scholar 

  41. Loetscher H, Pan YC, Lahm HW (1990) Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell 61: 351–359

    Article  PubMed  CAS  Google Scholar 

  42. Englemann H, Aderka D, Rubinstein M, Rotman D, Wallach D (1989) A tumor necrosis factor-binding protein purified to homogeneity from human urine protects cells from tumor necrosis factor toxicity. J Biol Chem 264: 11974–11980

    Google Scholar 

  43. Olsson I, Lantz M, Nilsson E (1989) Isolation and characterization of a tumor necrosis factor binding protein from urine. Eur J Haematol 42: 270–275

    Article  PubMed  CAS  Google Scholar 

  44. Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, Ettlinger RE, Cohen S, Koopman WJ, Mohler K et al (1997) Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. New Eng J Med 337: 141–147

    Article  PubMed  CAS  Google Scholar 

  45. Koller H, Thiem K, Siebler M (1996) Tumour necrosis factor-a increases intracellular Ca2+ and induces a depolarization in cultured astroglial cells. Brain 119: 2021–2027

    Article  PubMed  Google Scholar 

  46. Fine SM, Angel RA, Perry SW, Epstein LF, Rothstein JD, Dewhurst S, Gelbard HA (1996) Tumor necrosis factor-a inhibits glutamate uptake by primary human astrocytes. J Biol Chem 271(26): 15303–15306

    Article  PubMed  CAS  Google Scholar 

  47. Ding M, Hart RP, Jonakait FM (1995) Tumor necrosis factor-a induces substance P in sympathetic ganglia through sequential induction of Interleukin-1 and Leukemia Inhibitory Factor. J Neurobiol 28: 445–454

    Article  PubMed  CAS  Google Scholar 

  48. DeLeo JA, Colburn RW, Rickman AJ (1997) Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropathy. Brain Res 759: 50–57

    Article  PubMed  CAS  Google Scholar 

  49. Hickey, WF, Kimura H (1988) Perivascular microglia are bone marrow derived and present antigen in vivo. Science 239: 290–292

    Article  PubMed  CAS  Google Scholar 

  50. Streit WJ, and Kincaid-Colton CA (1995) The brain’s immune system. Scientific Amer Nov: 54–61

    Google Scholar 

  51. Meller ST, Dykstra C, Grsybicki, Murphy S, Gebhart GF (1994) The possible role of glia in nociceptive processing and hyperalgesia in the spinal cord of the rat. Neuropharm 33: 1471–1478

    Article  CAS  Google Scholar 

  52. Garrison CJ, Dougherty PM, Kajander KC, Carlton SM (1991) Staining of glial fibrillary acidic protein (GFAP) in lumbar spinal cord increases following a sciatic nerve constriction injury. Brain Res 565: 1–7

    Article  PubMed  CAS  Google Scholar 

  53. Hajos F, Csillik B, Knyihar-Csillik E (1990) Alterations in glial fibrillary acidic protein immunoreactivity in the upper dorsal horn of the rat spinal cord in the course of trans-ganglionic atrophy and regenerative proliferation. Neurosci Lett 17: 8–13

    Article  Google Scholar 

  54. Tetzlaff W, Graeber MB, Bisby MA, Kreutzberg GW (1988) Increased glial fibrillary protein synthesis in astrocytes during retrograde reaction of the rat facial nucleus. Glia 1: 90–95

    Article  PubMed  CAS  Google Scholar 

  55. Norris JG, Benveniste EN (1993) Interleukin-6 production by astrocytes: Induction by the neurotransmitter norepinephrine. J Neurosci 45:137–146

    CAS  Google Scholar 

  56. Chung JM, Leem JW, Kim SH (1992) Somatic afferent fibers which continuously discharge after being isolated from their receptors. Brain Res 599: 29–33

    Article  PubMed  CAS  Google Scholar 

  57. Korenman EMD, Devor M (1981) Ectopic adrenergic sensitivity in damaged peripheral nerve axons in the rat. Exp Neurol 72: 63–81.

    Article  PubMed  CAS  Google Scholar 

  58. McLachlan EM, Janig W, Devor M, Michaelis M (1993) Peripheral nerve injury triggers noradrenergic sprouting within the dorsal root ganglia. Nature 363: 543–545

    Article  PubMed  CAS  Google Scholar 

  59. Sato J, Perl ER (1993) Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury. Science 251:1608–1610

    Article  Google Scholar 

  60. Ventimiglia R, Green MI, Geller HM (1987) Localization of f3-adrenergic receptors on differentiated cells of the central nervous system in culture. Proc Natl Acad Sci 84: 5073–5077

    Article  PubMed  CAS  Google Scholar 

  61. Furukawa S, Furukawa Y, Satoyoshi E, Hayashi K (1987) Regulation of nerve growth factor synthesis/secretion by catecholamine in cultured mouse astroglial cells. Biochem Biophys Res Commun 147: 1048–1054

    Article  PubMed  CAS  Google Scholar 

  62. Frohman EM, Vayuvegula B, van den Noort S, Gupta S (1988) Norepinephrine inhibits gamma-interferon-induced MHC class II (Ia) antigen expression on cultured brain astrocytes. J Neuroimmunol 17: 89–101

    Article  PubMed  CAS  Google Scholar 

  63. Kashiba H, Senba E, Kawai Y, Ueda Y, Tohyama (1992) Axonal blockade induces the expression of vasoactive intestinal peptide and galanin in rat dorsal root ganglion neurons. Brain Res 577: 19–28

    Article  PubMed  CAS  Google Scholar 

  64. Sontheimer H, Black JA, Waxman SG (1996) Voltage-gated Na+ channels in glia: properties and possible functions. Trends Neurosci 19: 325–331

    Article  PubMed  CAS  Google Scholar 

  65. Steinhauser C, Gallo V (1996) News on glutamate receptors in glial cells. Trends Neurosci 19: 339–345

    Article  PubMed  CAS  Google Scholar 

  66. Glabinshi AR, Balasingam V, Tani M, Kunket SL, Strieter RM, Yong VW, Ransohoff RM (1996) Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain. J Immunol 156: 4363–4368

    Google Scholar 

  67. Hurwitz AA, Lyman WD, Berman JW (1995) Tumor necrosis factor alpha and transforming growth factor beta upregulate astrocyte expression of monocyte chemoattractant protein-1. J Neuroimmunol 57: 193–198

    Article  PubMed  CAS  Google Scholar 

  68. Garrison CJ, Dougherty PM, Carlton SM (1994) GFAP expression in lumbar spinal cord of naive and neuropathic rats treated with MK-801. Exp Neurol 129: 237–243

    Article  PubMed  CAS  Google Scholar 

  69. Watkins LR, Marin D, Ulrich P, Tracey KJ, Maier SF (1997) Evidence for the involvement of spinal cord glia in subcutaneous formalin induced hyperalgesia in the rat. Pain 71: 225–235

    Article  PubMed  CAS  Google Scholar 

  70. Xiao WH, Wagner R, Myers RR, Sorkin LS (1996) TNF-a applied to the sciatic nerve trunk elicits background firing in nociceptive primary afferent fibers. 8th World Congress on Pain. Vancouver, BC, Canada

    Google Scholar 

  71. Wagner R, Myers RR (1996) Endoneurial injection of TNF alpha produces neuropathic behaviors. Neuro Report 7: 2897–2901

    CAS  Google Scholar 

  72. Bennett GJ, Laird JMA (1992) Central changes contributing to neuropathic hyperalgesia. In: Willis, Jr. WD (ed): Hyperalgesia and allodynia. Raven Press, New York, 305–310

    Google Scholar 

  73. Wagner R, DeLeo JA, Coombs DW, Colburn RW, Willenbring S, Fromm C (1993) Spinal dynorphin bilaterally increases in a rat neuropathic pain model. Brain Res 629: 323–326

    Article  PubMed  CAS  Google Scholar 

  74. Wall PD (1983) Alterations in the central nervous system after deafferentation: Connectivity control. In: Bonica J (ed): Advances in pain research and therapy. Raven Press, New York, 677–689

    Google Scholar 

  75. Lewin GR, Rueff A, Mendell LM (1994) Peripheral and central mechanisms of NGFinduced hyperalgesia. Eur J Neurosci 6: 1903–1912

    Article  PubMed  CAS  Google Scholar 

  76. Strijbos P, Rothwell NJ (1995) Interleukin-43 attenuates excitatory amino acid-induced neurodegeneration in vitro: involvement of nerve growth factor. J Neurosci 15: 3468–3474

    PubMed  CAS  Google Scholar 

  77. Lewin GR, Mendell LM (1993) Nerve growth factor and nociception. TINS 16: 353–365

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Basel AG

About this chapter

Cite this chapter

DeLeo, J.A., Colburn, R.W. (1999). Proinflammatory cytokines and glial cells: Their role in neuropathic pain. In: Watkins, L.R., Maier, S.F. (eds) Cytokines and Pain. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8749-6_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-8749-6_7

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9756-3

  • Online ISBN: 978-3-0348-8749-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics