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Up-regulation of p55 TNF alpha-receptor in dorsal root ganglia neurons following lumbar facet joint injury in rats

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Abstract

The rat L5/6 facet joint is multisegmentally innervated from the L1 to L6 dorsal root ganglia (DRG). Tumor necrosis factor (TNF) is a known mediator of inflammation. It has been reported that satellite cells are activated, produce TNF and surround DRG neurons innervating L5/6 facet joints after facet injury. In the current study, changes in TNF receptor (p55) expression in DRG neurons innervating the L5/6 facet joint following facet joint injury were investigated in rats using a retrograde neurotransport method followed by immunohistochemistry. Twenty rats were used for this study. Two crystals of Fluorogold (FG; neurotracer) were applied into the L5/6 facet joint. Seven days after surgery, the dorsal portion of the capsule was cut in the injured group (injured group n = 10). No injury was performed in the non-injured group (n = 10). Fourteen days after the first application of FG, bilateral DRGs from T13 to L6 levels were resected and sectioned. They were subsequently processed for p55 immunohistochemistry. The number of FG labeled neurons and number of FG labeled p55-immunoreactive (IR) neurons were counted. FG labeled DRG neurons innervating the L5/6 facet joint were distributed from ipsilateral L1 to L6 levels. Of FG labeled neurons, the ratio of DRG neurons immunoreactive for p55 in the injured group (50%) was significantly higher than that in the non-injured group (13%). The ratio of p55-IR neurons of FG labeled DRG neurons was significantly higher in total L1 and L2 DRGs than that in total L3, 4, 5 and 6 DRGs in the injured group (L1 and 2 DRG, 67%; L3, 4, 5 and 6 DRG, 37%, percentages of the total number of p55-IR neurons at L1 and L2 level or L3–6 level/the total number of FG-labeled neurons at L1 and L2 level or L3–6 level). These data suggest that up-regulation of p55 in DRG neurons may be involved in the sensory transmission from facet joint injury. Regulation of p55 in DRG neurons innervating the facet joint was different between upper DRG innervated via the paravertebral sympathetic trunks and lower DRG innervated via other direct routes.

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References

  1. Bartholdi D, Schwab ME (1997) Expression of pro-inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: an in situ hybridization study. Eur J Neurosci 9:1422–1438

    Article  PubMed  CAS  Google Scholar 

  2. Bogduk N, Long DM (1979) The anatomy of the so-called “articular nerves” and their relationship to facet denervation in the treatment of low back pain. J Neurosurg 51:172–177

    Article  PubMed  CAS  Google Scholar 

  3. Bogduk N (1983) The innervation of the lumbar spine. Spine 8:286–293

    Article  PubMed  CAS  Google Scholar 

  4. Botchkina GI, Meistrell ME, Botchkina IL, Tracey KJ (1997) Expression of TNF and TNF receptors (p55 and p75) in the rat brain after focal cerebral ischemia. Mol Med 3:765–781

    PubMed  CAS  Google Scholar 

  5. Cavanaugh JM, el-Bohy A, Hardy WN, Getchell TV, Getchell ML, King AI (1989) Sensory innervation of soft tissues of the lumbar spine in the rat. J Orthop Res 7:378–388

    Article  PubMed  CAS  Google Scholar 

  6. Ding M, Hart RP, Jonakait GM (1995) Tumor necrosis factor-alpha 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 

  7. Fenzi F, Benedetti MD, Moretto G, Rizzuto N (2001) Glial cell and macrophage reactions in rat spinal ganglion after peripheral nerve lesions: an immunocytochemical and morphometric study. Arch Ital Biol 139:357–365

    PubMed  CAS  Google Scholar 

  8. Hökfelt T (1991) Neuropeptides in perspective: the last ten years. Neuron 7:867–879

    Article  PubMed  Google Scholar 

  9. Muñoz-Fernandez MA, Fresno M (1998) The role of tumour necrosis factor, interleukin 6, interferon-gamma and inducible nitric oxide synthase in the development and pathology of the nervous system. Prog Neurobiol 56:307–340

    Article  PubMed  Google Scholar 

  10. Mooney V, Robertson J (1976) The facet syndrome. Clin Orthop Res 115:149–156

    Google Scholar 

  11. Miyagi M, Ohtori S, Ishikawa T, Aoki Y, Ozawa T, Doya H, Saito T, Moriya H,Takahashi K (2006) Up-regulation of TNF alpha in DRG satellite cells following lumbar facet joint injury in rats. Eur Spine J 15:953–958

    Article  PubMed  Google Scholar 

  12. Myers RR, Wagner R, Sorkin LS (1999) Hyperalgesic actions of cytokines on peripheral nerves. In: Watkins LR, Maier SF (eds) Cytokines and Pain. Birkhauser, Boston, pp 133–157

  13. Ohtori S, Takahashi K, Chiba T, Yamagata M, Sameda H, Moriya H (2000) Substance P and calcitonin gene-related peptide immunoreactive sensory DRG neurons innervating the lumbar facet joints in rats. Auton Neurosci 86:13–17

    Article  PubMed  CAS  Google Scholar 

  14. Ohtori S, Takahashi K, Chiba T, Yamagata M, Sameda H, Moriya H (2001) Phenotypic inflammation switch in rats shown by calcitonin gene-related peptide immunoreactive dorsal root ganglion neurons innervating the lumbar facet joints. Spine 26:1009–1013

    Article  PubMed  CAS  Google Scholar 

  15. Ohtori S, Takahashi K, Moriya H (2002) Inflammatory pain mediated by a phenotypic switch in brain-derived neurotrophic factor immunoreactive dorsal root ganglion neurons innervating the lumbar facet joints in rats. Neurosci Lett 323:129–132

    PubMed  CAS  Google Scholar 

  16. Ohtori S, Takahashi K, Moriya H (2003) Calcitonin gene-related peptide immunoreactive DRG neurons innervating the cervical facet joints show phenotypic switch in cervical facet injury in rats. Eur Spine J 12:211–215

    Article  PubMed  Google Scholar 

  17. Ohtori S, Takahashi K, Moriya H, Myers RR (2004) TNF-alpha and TNF-alpha receptor type 1 upregulation in glia and neurons after peripheral nerve injury: studies in murine DRG and spinal cord. Spine 29:1082–1088

    Article  PubMed  Google Scholar 

  18. Shubayev VI, Myers RR (2001) Axonal transport of TNF-alpha in painful neuropathy: distribution of ligand tracer and TNF receptors. J Neuroimmunol 114:48–56

    Article  PubMed  CAS  Google Scholar 

  19. Shubayev VI, Myers RR (2002) Anterograde TNF alpha transport from rat dorsal root ganglion to spinal cord and injured sciatic nerve. Neurosci Lett 320:99–101

    Article  PubMed  CAS  Google Scholar 

  20. Smith CA, Farrah T, Goodwin RG (1994) The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 76:959–962

    Article  PubMed  CAS  Google Scholar 

  21. Suseki K, Takahashi Y, Takahashi K, Chiba T, Tanaka K, Moriya H (1996) CGRP-immunoreactive nerve fibers projecting to lumbar facet joints through the paravertebral sympathetic trunk in rats. Neurosci Lett 221:41–44

    Article  PubMed  CAS  Google Scholar 

  22. Suseki K, Takahashi Y, Takahashi K, Chiba T, Tanaka K, Morinaga T, Nakamura S, Moriya H (1997) Innervation of the lumbar facet joints. Origin and functions. Spine 22:477–485

    Article  PubMed  CAS  Google Scholar 

  23. Wagner R, Myers RR (1996) Schwann cells produce TNF-alpha: expression in injured and non-injured nerves. Neurosci 73:625–629

    Article  CAS  Google Scholar 

  24. Wagner R, Myers RR (1996) Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. Neuroreport 7:2897–2901

    Article  PubMed  CAS  Google Scholar 

  25. Yamashita T, Cavanaugh JM, el-Bohy AA, Getchell TV, King AI (1990) Mechanosensitive afferent units in the lumbar facet joint. J Bone Joint Surg Am 72:865–870

    PubMed  CAS  Google Scholar 

  26. Zhou XF, Deng YS, Chie E, Xue Q, Zhong JH, McLachlan EM, Rush RA, Xian CJ (1999) Satellite-cell-derived nerve growth factor and neurotrophin-3 are involved in noradrenergic sprouting in the dorsal root ganglia following peripheral nerve injury in the rat. Eur J Neurosci 11:1711–1722

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Yoshihiro Sakuma, Seiji Ohtori, Masayuki Miyagi, Tetsu Ishikawa, Gen Inoue, Hideo Doya, Takana Koshi, Toshinori Ito, Masaomi Yamashita, Kazuyo Yamauchi, Munetaka Suzuki, Hideshige Moriya & Kazuhisa Takahashi

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  1. Yoshihiro Sakuma
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  2. Seiji Ohtori
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  3. Masayuki Miyagi
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  4. Tetsu Ishikawa
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  5. Gen Inoue
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  6. Hideo Doya
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  7. Takana Koshi
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  8. Toshinori Ito
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  9. Masaomi Yamashita
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  10. Kazuyo Yamauchi
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  11. Munetaka Suzuki
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  12. Hideshige Moriya
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  13. Kazuhisa Takahashi
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Corresponding author

Correspondence to Seiji Ohtori.

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Y. Sakuma and S. Ohtori contributed equally to this work.

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Sakuma, Y., Ohtori, S., Miyagi, M. et al. Up-regulation of p55 TNF alpha-receptor in dorsal root ganglia neurons following lumbar facet joint injury in rats. Eur Spine J 16, 1273–1278 (2007). https://doi.org/10.1007/s00586-007-0365-3

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  • DOI: https://doi.org/10.1007/s00586-007-0365-3

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