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Dorsal root ganglion compression as an animal model of sciatica and low back pain

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Abstract

As sciatica and low back pain are among the most common medical complaints, many studies have duplicated these conditions in animals. Chronic compression of the dorsal root ganglion (CCD) is one of these models. The surgery is simple: after exposing the L4/L5 intervertebral foramina, stainless steel rods are implanted unilaterally, one rod for each vertebra, to chronically compress the lumbar dorsal root ganglion (DRG). Then, CCD can be used to simulate the clinical conditions caused by stenosis, such as a laterally herniated disc or foraminal stenosis. As the intraforaminal implantation of a rod results in neuronal somal hyperexcitability and spontaneous action potentials associated with hyperalgesia, spontaneous pain, and mechanical allodynia, CCD provides an animal model that mimics radicular pain in humans. This review concerns the mechanisms of neuronal hyperexcitability, focusing on various patterns of spontaneous discharge including one possible pain signal for mechanical allodynia — evoked bursting. Also, new data regarding its significant property of maintaining peripheral input are also discussed. Investigations using this animal model will enhance our understanding of the neural mechanisms for low back pain and sciatica. Furthermore, the peripheral location of the DRG facilitates its use as a locus for controlling pain with minimal central effects, in the hope of ultimately uncovering analgesics that block neuropathic pain without influencing physiological pain.

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References

  1. Mogil JS. Animal models of pain: progress and challenges. Nat Rev Neurosci 2009, 10(4): 283–294.

    Article  PubMed  CAS  Google Scholar 

  2. Hu SJ, Xing JL. An experimental model for chronic compression of dorsal root ganglion produced by intervertebral foramen stenosis in the rat. Pain 1998, 77(1): 15–23.

    Article  PubMed  CAS  Google Scholar 

  3. Song XJ, Hu SJ, Greenquist KW, Zhang JM, LaMotte RH. Mechanical and thermal hyperalgesia and ectopic neuronal discharge after chronic compression of dorsal root ganglia. J Neurophysiol 1999, 82(6): 3347–3358.

    PubMed  CAS  Google Scholar 

  4. Ochoa JL, Yarnitsky D. Mechanical hyperalgesias in neuropathic pain patients: dynamic and static subtypes. Ann Neurol 1993, 33(5): 465–472.

    Article  PubMed  CAS  Google Scholar 

  5. Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992, 50(3): 355–363.

    Article  PubMed  CAS  Google Scholar 

  6. Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988, 33(1): 87–107.

    Article  PubMed  CAS  Google Scholar 

  7. Seltzer Z, Dubner R, Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 1990, 43(2): 205–218.

    Article  PubMed  CAS  Google Scholar 

  8. Song XJ, Vizcarra C, Xu DS, Rupert RL, Wong ZN. Hyperalgesia and neural excitability following injuries to central and peripheral branches of axons and somata of dorsal root ganglion neurons. J Neurophysiol 2003, 89(4): 2185–2193.

    Article  PubMed  Google Scholar 

  9. Xing JL, Hu SJ, Long KP. Subthreshold membrane potential oscillations of type A neurons in injured DRG. Brain Res 2001, 901(1–2): 128–136.

    Article  PubMed  CAS  Google Scholar 

  10. Ma C, Greenquist KW, Lamotte RH. Inflammatory mediators enhance the excitability of chronically compressed dorsal root ganglion neurons. J Neurophysiol 2006, 95(4): 2098–2107.

    Article  PubMed  CAS  Google Scholar 

  11. Ma C, LaMotte RH. Enhanced excitability of dissociated primary sensory neurons after chronic compression of the dorsal root ganglion in the rat. Pain 2005, 113(1-2): 106–112.

    Article  PubMed  Google Scholar 

  12. Zheng JH, Walters ET, Song XJ. Dissociation of dorsal root ganglion neurons induces hyperexcitability that is maintained by increased responsiveness to cAMP and cGMP. J Neurophysiol 2007, 97(1): 15–25.

    Article  PubMed  CAS  Google Scholar 

  13. LaMotte RH. Acutely dissociated sensory neurons: normal or neuropathic? Focus on: ”Dissociation of dorsal root ganglion neurons induces hyperexcitability that is maintained by increased responsiveness to cAMP and cGMP”. J Neurophysiol 2007, 97(1): 1–2.

    Article  PubMed  CAS  Google Scholar 

  14. Xing JL, Hu SJ, Xu H, Han S, Wan YH. Subthreshold membrane oscillations underlying integer multiples firing from injured sensory neurons. Neuroreport 2001, 12(6): 1311–1313.

    Article  PubMed  CAS  Google Scholar 

  15. Xing JL, Hu SJ, Jian Z, Duan JH. Subthreshold membrane potential oscillation mediates the excitatory effect of norepinephrine in chronically compressed dorsal root ganglion neurons in the rat. Pain 2003, 105(1-2): 177–183.

    Article  PubMed  CAS  Google Scholar 

  16. Liu CN, Michaelis M, Amir R, Devor M. Spinal nerve injury enhances subthreshold membrane potential oscillations in DRG neurons: relation to neuropathic pain. J Neurophysiol 2000, 84(1): 205–215.

    PubMed  CAS  Google Scholar 

  17. Hutcheon B, Yarom Y. Resonance, oscillation and the intrinsic frequency preferences of neurons. Trends Neurosci 2000, 23(5): 216–222.

    Article  PubMed  CAS  Google Scholar 

  18. Wang YY, Wen ZH, Duan JH, Zhu JL, Wang WT, Dong H, et al. Noise enhances subthreshold oscillations in injured primary sensory neurons. Neurosignals 2011, 19(1): 54–62.

    Article  PubMed  Google Scholar 

  19. Ma C, LaMotte RH. Multiple sites for generation of ectopic spontaneous activity in neurons of the chronically compressed dorsal root ganglion. J Neurosci 2007, 27(51): 14059–14068.

    Article  PubMed  CAS  Google Scholar 

  20. Yu Y, Shu Y, McCormick DA. Cortical action potential backpropagation explains spike threshold variability and rapid-onset kinetics. J Neurosci 2008, 28(29): 7260–7272.

    Article  PubMed  CAS  Google Scholar 

  21. Hu SJ, Song XJ, Greenquist KW, Zhang JM, LaMotte RH. Protein kinase A modulates spontaneous activity in chronically compressed dorsal root ganglion neurons in the rat. Pain 2001, 94(1): 39–46.

    Article  PubMed  CAS  Google Scholar 

  22. Song XJ, Wang ZB, Gan Q, Walters ET. cAMP and cGMP contribute to sensory neuron hyperexcitability and hyperalgesia in rats with dorsal root ganglia compression. J Neurophysiol 2006, 95(1): 479–492.

    Article  PubMed  CAS  Google Scholar 

  23. Gao YJ, Ji RR. Light touch induces ERK activation in superficial dorsal horn neurons after inflammation: involvement of spinal astrocytes and JNK signaling in touch-evoked central sensitization and mechanical allodynia. J Neurochem 2010, 115(2): 505–514.

    Article  PubMed  CAS  Google Scholar 

  24. Zhang Y, Cai G, Ni X, Sun J. The role of ERK activation in the neuronal excitability in the chronically compressed dorsal root ganglia. Neurosci Lett 2007, 419(2): 153–157.

    Article  PubMed  CAS  Google Scholar 

  25. Ding XL, Wang YH, Ning LP, Zhang Y, Ge HY, Jiang H, et al. Involvement of TRPV4-NO-cGMP-PKG pathways in the development of thermal hyperalgesia following chronic compression of the dorsal root ganglion in rats. Behav Brain Res 2010, 208(1): 194–201.

    Article  PubMed  CAS  Google Scholar 

  26. Zhang L, Berta T, Xu ZZ, Liu T, Park JY, Ji RR. TNF-α contributes to spinal cord synaptic plasticity and inflammatory pain: distinct role of TNF receptor subtypes 1 and 2. Pain 2011, 152(2): 419–427.

    Article  PubMed  CAS  Google Scholar 

  27. Liu B, Li H, Brull SJ, Zhang JM. Increased sensitivity of sensory neurons to tumor necrosis factor alpha in rats with chronic compression of the lumbar ganglia. J Neurophysiol 2002, 88(3): 1393–1399.

    Article  PubMed  CAS  Google Scholar 

  28. Homma Y, Brull SJ, Zhang JM. A comparison of chronic pain behavior following local application of tumor necrosis factor alpha to the normal and mechanically compressed lumbar ganglia in the rat. Pain 2002, 95(3): 239–246.

    Article  PubMed  CAS  Google Scholar 

  29. Oh SB, Tran PB, Gillard SE, Hurley RW, Hammond DL, Miller RJ. Chemokines and glycoprotein120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J Neurosci 2001, 21(14): 5027–5035.

    PubMed  CAS  Google Scholar 

  30. White FA, Sun J, Waters SM, Ma C, Ren D, Ripsch M, et al. Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion. Proc Natl Acad Sci U S A 2005, 102(39): 14092–14097.

    Article  PubMed  CAS  Google Scholar 

  31. Wang CH, Zou LJ, Zhang YL, Jiao YF, Sun JH. The excitatory effects of the chemokine CCL2 on DRG somata are greater after an injury of the ganglion than after an injury of the spinal or peripheral nerve. Neurosci Lett 2010, 475(1): 48–52.

    Article  PubMed  CAS  Google Scholar 

  32. Gao YJ, Ji RR. Targeting astrocyte signaling for chronic pain. Neurotherapeutics 2010, 7(4): 482–493.

    Article  PubMed  CAS  Google Scholar 

  33. Austin PJ, Moalem-Taylor G. The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immunelike glial cells and cytokines. J Neuroimmunol 2010, 229(1–2): 26–50.

    Article  PubMed  CAS  Google Scholar 

  34. Hanani M. Satellite glial cells in sensory ganglia: from form to function. Brain Res Brain Res Rev 2005, 48(3): 457–476.

    Article  PubMed  CAS  Google Scholar 

  35. Zhang H, Mei X, Zhang P, Ma C, White FA, Donnelly DF, et al. Altered functional properties of satellite glial cells in compressed spinal ganglia. Glia 2009, 57(15): 1588–1599.

    Article  PubMed  Google Scholar 

  36. Jian Z, Xing JL, Yang GS, Hu SJ. A novel bursting mechanism of type A neurons in injured dorsal root ganglia. Neurosignals 2004, 13(3): 150–156.

    Article  PubMed  CAS  Google Scholar 

  37. Izhikevich EM. The geometry of excitability and bursting. In: Sejnowski TJ, Toggio TA (Eds.). Dynamical Systems in Neuroscience. Cambridge, MA: MIT Press, 2006.

    Google Scholar 

  38. Song Y, Li HM, Xie RG, Yue ZF, Song XJ, Hu SJ, et al. Evoked bursting in injured Aβ dorsal root ganglion neurons: a mechanism underlying tactile allodynia. Pain 2012, 153(3): 657–665.

    Article  PubMed  Google Scholar 

  39. Han HC, Lee DH, Chung JM. Characteristics of ectopic discharges in a rat neuropathic pain model. Pain 2000, 84(2-3): 253–261.

    Article  PubMed  CAS  Google Scholar 

  40. Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain 1992, 48(2): 261–268.

    Article  PubMed  CAS  Google Scholar 

  41. Gracely RH, Lynch SA, Bennett GJ. Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 1992, 51(2): 175–194.

    Article  PubMed  CAS  Google Scholar 

  42. Sheen K, Chung JM. Signs of neuropathic pain depend on signals from injured nerve fibers in a rat model. Brain Res 1993, 610(1): 62–68.

    Article  PubMed  CAS  Google Scholar 

  43. Yoon YW, Na HS, Chung JM. Contributions of injured and intact afferents to neuropathic pain in an experimental rat model. Pain 1996, 64(1): 27–36.

    Article  PubMed  CAS  Google Scholar 

  44. Sandkühler J. Models and mechanisms of hyperalgesia and allodynia. Physiol Rev 2009, 89(2): 707–758.

    Article  PubMed  Google Scholar 

  45. Devor M. Ectopic discharge in Abeta afferents as a source of neuropathic pain. Exp Brain Res 2009, 196(1): 115–128.

    Article  PubMed  CAS  Google Scholar 

  46. Pitcher GM, Henry JL. Nociceptive response to innocuous mechanical stimulation is mediated via myelinated afferents and NK-1 receptor activation in a rat model of neuropathic pain. Exp Neurol 2004, 186(2): 173–197.

    Article  PubMed  CAS  Google Scholar 

  47. Yao H, Donnelly DF, Ma C, LaMotte RH. Upregulation of the hyperpolarization-activated cation current after chronic compression of the dorsal root ganglion. J Neurosci 2003, 23(6): 2069–2074.

    PubMed  CAS  Google Scholar 

  48. Tan ZY, Donnelly DF, LaMotte RH. Effects of a chronic compression of the dorsal root ganglion on voltage-gated Na+ and K+ currents in cutaneous afferent neurons. J Neurophysiol 2006, 95(2): 1115–1123.

    Article  PubMed  CAS  Google Scholar 

  49. Fan N, Donnelly DF, LaMotte RH. Chronic compression of mouse dorsal root ganglion alters voltage-gated sodium and potassium currents in medium-sized dorsal root ganglion neurons. J Neurophysiol 2011, 106(6): 3067–3072.

    Article  PubMed  CAS  Google Scholar 

  50. Dong H, Fan YH, Wang YY, Wang WT, Hu SJ. Lidocaine suppresses subthreshold oscillations by inhibiting persistent Na+ current in injured dorsal root ganglion neurons. Physiol Res 2008, 57(4): 639–645.

    PubMed  CAS  Google Scholar 

  51. Yang RH, Wang WT, Chen JY, Xie RG, Hu SJ. Gabapentin selectively reduces persistent sodium current in injured type-A dorsal root ganglion neurons. Pain 2009, 143(1-2): 48–55.

    Article  PubMed  CAS  Google Scholar 

  52. Wall PD, Devor M, Inbal R, Scadding JW, Schonfeld D, Seltzer Z, et al. Autotomy following peripheral nerve lesions: experimental anaesthesia dolorosa. Pain 1979, 7(2): 103–111.

    Article  PubMed  CAS  Google Scholar 

  53. Wall PD, Scadding JW, Tomkiewicz MM. The production and prevention of experimental anesthesia dolorosa. Pain 1979, 6(2): 175–182.

    Article  PubMed  CAS  Google Scholar 

  54. Decosterd I, Woolf CJ. Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 2000, 87(2): 149–158.

    Article  PubMed  CAS  Google Scholar 

  55. Shir Y, Seltzer Z. Effects of sympathectomy in a model of causal-giform pain produced by partial sciatic nerve injury in rats. Pain 1991, 45(3): 309–320.

    Article  PubMed  CAS  Google Scholar 

  56. Seltzer Z, Dubner R, Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 1990, 43(2): 205–218.

    Article  PubMed  CAS  Google Scholar 

  57. Wall PD, Devor M. Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats. Pain 1983, 17(4): 321–339.

    Article  PubMed  CAS  Google Scholar 

  58. Liu CN, Michaelis M, Amir R, Devor M. Spinal nerve injury enhances subthreshold membrane potential oscillations in DRG neurons: relation to neuropathic pain. J Neurophysiol 2000, 84(1): 205–215.

    PubMed  CAS  Google Scholar 

  59. Xie W, Strong JA, Meij JT, Zhang JM, Yu L. Neuropathic pain: early spontaneous afferent activity is the trigger. Pain 2005, 116(3): 243–256.

    Article  PubMed  Google Scholar 

  60. Andersson GB. Epidemiological features of chronic low-back pain. Lancet 1999, 354(9178): 581–585.

    Article  PubMed  CAS  Google Scholar 

  61. Cornefjord M, Sato K, Olmarker K, Rydevik B, Nordborg C. A model for chronic nerve root compression studies. Presentation of a porcine model for controlled, slow-onset compression with analyses of anatomic aspects, compression onset rate, and morphologic and neurophysiologic effects. Spine (Phila Pa 1976) 1997, 22(9): 946–957.

    Article  CAS  Google Scholar 

  62. Winkelstein BA, Weinstein JN, DeLeo JA. The role of mechanical deformation in lumbar radiculopathy: an in vivo model. Spine (Phila Pa 1976) 2002, 27(1): 27–33.

    Article  Google Scholar 

  63. Song XJ, Xu DS, Vizcarra C, Rupert RL. Onset and recovery of hyperalgesia and hyperexcitability of sensory neurons following intervertebral foramen volume reduction and restoration. J Manipulative Physiol Ther 2003, 26(7): 426–436.

    Article  PubMed  Google Scholar 

  64. Gu X, Yang L, Wang S, Sung B, Lim G, Mao J, et al. A rat model of radicular pain induced by chronic compression of lumbar dorsal root ganglion with SURGIFLO. Anesthesiology 2008, 108(1): 113–121.

    Article  PubMed  Google Scholar 

  65. Carette S, Fehlings MG. Clinical practice. Cervical radiculopathy. N Engl J Med 2005, 353(4): 392–399.

    Article  PubMed  CAS  Google Scholar 

  66. Yeung AT, Yeung CA. Minimally invasive techniques for the management of lumbar disc herniation. Orthop Clin North Am 2007, 38(3): 363–372.

    Article  PubMed  Google Scholar 

  67. Hou SX, Tang JG, Chen HS, Chen J. Chronic inflammation and compression of the dorsal root contribute to sciatica induced by the intervertebral disc herniation in rats. Pain 2003, 105(1–2): 255–264.

    Article  PubMed  Google Scholar 

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Correspondence to Jun-Ling Xing.

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Lin, XY., Yang, J., Li, HM. et al. Dorsal root ganglion compression as an animal model of sciatica and low back pain. Neurosci. Bull. 28, 618–630 (2012). https://doi.org/10.1007/s12264-012-1276-9

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  • DOI: https://doi.org/10.1007/s12264-012-1276-9

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